Nampt inhibitors

ABSTRACT

Disclosed are compounds which inhibit the activity of NAMPT, compositions containing the compounds and methods of treating diseases during which NAMPT is expressed.

This application claims priority to U.S. Provisional Application Ser. No. 61/645,692, filed May 11, 2012, U.S. Provisional Application Ser. No. 61/719,013, filed Oct. 26, 2012, and U.S. Provisional Application Ser. No. 61/779,756, filed Mar. 13, 2013, which are incorporated by reference in their entirety.

FIELD OF THE INVENTION

This invention pertains to compounds which inhibit the activity of NAMPT, compositions containing the compounds, and methods of treating diseases during which NAMPT is expressed.

BACKGROUND OF THE INVENTION

NAD+ (nicotinamide adenine dinucleotide) is a coenzyme that plays a critical role in many physiologically essential processes (Ziegkel, M. Eur. J. Biochem. 267, 1550-1564, 2000). NAD is necessary for several signaling pathways including among others poly ADP-ribosylation in DNA repair, mono-ADP-ribosylation in both the immune system and G-protein-coupled signaling, and NAD is also required by sirtuins for their deacetylase activity (Garten, A. et al Trends in Endocrinology and Metabolism, 20, 130-138, 2008).

NAMPT (also known as pre-B-cell-colony-enhancing factor (PBEF) and visfatin) is an enzyme that catalyzes the phosphoribosylation of nicotinamide and is the rate-limiting enzyme in one of two pathways that salvage NAD.

Increasing evidence suggests that NAMPT inhibitors have potential as anticancer agents. Cancer cells have a higher basal turnover of NAD and also display higher energy requirements compared with normal cells. Additionally, increased NAMPT expression has been reported in colorectal cancer (Van Beijnum, J. R. et al Int. J. Cancer 101, 118-127, 2002) and NAMPT is involved in angiogenesis (Kim, S R et al. Biochem. Biophys. Res. Commun. 357, 150-156, 2007). Small-molecule inhibitors of NAMPT have been shown to cause depletion of intracellular NAD+ levels and ultimately induce tumor cell death (Hansen, C M et al. Anticancer Res. 20, 42111-4220, 2000) as well as inhibit tumor growth in xenograft models (Olese, U. H. et al. Mol Cancer Ther. 9, 1609-1617, 2010).

NAMPT inhibitors also have potential as therapeutic agents in inflammatory and metabolic disorders (Galli, M. et al Cancer Res. 70, 8-11, 2010). For example, NAMPT is the predominant enzyme in T and B lymphocytes. Selective inhibition of NAMPT leads to NAD+ depletion in lymphocytes blocking the expansion that accompanies autoimmune disease progression whereas cell types expressing the other NAD+ generating pathways might be spared. A small molecule NAMPT inhibitor (FK866) has been shown to selectively block proliferation and induce apoptosis of activated T cells and was efficacious in animal models of arthritis (collagen induced arthritis) (Busso, N. et al. Plos One 3, e2267, 2008). FK866 ameliorated the manifestations of experimental autoimmune encephalomyelitis (EAE), a model of T-cell mediated autoimmune disorders. (Bruzzone, S et al. Plos One 4, e7897, 2009). NaMPT activity increases NF-kB transcriptional activity in human vascular endothelial cell, resulting in MMP-2 and MMP-9 activation, suggesting a role for NAMPT inhibitors in the prevention of inflammatory mediated complications of obesity and type 2 diabetes (Adya, R. et. Al. Diabetes Care, 31, 758-760, 2008).

SUMMARY OF THE INVENTION

One embodiment of this invention, therefore, pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (IC)

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is C(O)NH, or NHC(O);

Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl;

R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I;

R² is independently selected from the group consisting of C₄-C₆-alkyl, C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl, and 5-6 membered heteroaryl; wherein each R² C₄-C₆-alkyl, C₄-C₆-alkenyl, and C₄-C₆-alkynyl is substituted with one or more substituents independently selected from the group consisting of R³, OR³, SR³, S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂, NHR³, N(R³)₂, NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³, NR³C(O)OR³, NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³, NR³C(O)N(R³)₂, C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³, C(O)NHSO₂R³, C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I;

R³, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and heterocyclyl; wherein each R³ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁵, OR⁵, SR⁵, S(O)R⁵, SO₂R⁵, C(O)R⁵, CO(O)R⁵, OC(O)R⁵, OC(O)OR⁵, NH₂, NHR⁵, N(R⁵)₂, NHC(O)R⁵, NR⁵C(O)R⁵, NHS(O)₂R⁵, NR⁵S(O)₂R⁵, NHC(O)OR⁵, NR⁵C(O)OR⁵, NHC(O)NH₂, NHC(O)NHR⁵, NHC(O)N(R⁵)₂, NR⁵C(O)NHR⁵, NR⁵C(O)N(R⁵)₂, C(O)NH₂, C(O)NHR⁵, C(O)N(R⁵)₂, C(O)NHOH, C(O)NHOR⁵, C(O)NHSO₂R⁵, C(O)NR⁵SO₂R⁵, SO₂NH₂, SO₂NHR⁵, SO₂N(R⁵)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁵, C(N)N(R⁵)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R³ aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁶, OR⁶, SR⁶, S(O)R⁶, SO₂R⁶, C(O)R⁶, CO(O)R⁶, OC(O)R⁶, OC(O)OR⁶, NH₂, NHR⁶, N(R⁶)₂, NHC(O)R⁶, NR⁶C(O)R⁶, NHS(O)₂R⁶, NR⁶S(O)₂R⁶, NHC(O)OR⁶, NR⁶C(O)OR⁶, NHC(O)NH₂, NHC(O)NHR⁶, NHC(O)N(R⁶)₂, NR⁶C(O)NHR⁶, NR⁶C(O)N(R⁶)₂, C(O)NH₂, C(O)NHR⁶, C(O)N(R⁶)₂, C(O)NHOH, C(O)NHOR⁶, C(O)NHSO₂R⁶, C(O)NR⁶SO₂R⁶, SO₂NH₂, SO₂NHR⁶, SO₂N(R⁶)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁶, C(N)N(R⁶)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I;

R⁵, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁵ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁸, OR⁸, SR⁸, S(O)R⁸, SO₂R⁸, NHR⁸, N(R⁸)₂, C(O)R⁸, C(O)NH₂, C(O)NHR⁸, C(O)N(R⁸)₂, NHC(O)R⁸, NR⁸C(O)R⁸, NHSO₂R⁸, NHC(O)OR⁸, SO₂NH₂, SO₂NHR⁸, SO₂N(R⁸)₂, NHC(O)NH₂, NHC(O)NHR⁸, OH, (O), C(O)OH, N₃, CN, NH₂, F, Cl, Br and I;

R⁶, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁶ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁹, OR⁹, SR⁹, S(O)R⁹, SO₂R⁹, NHR⁹, N(R⁹)₂, C(O)R⁹, C(O)NH₂, C(O)NHR⁹, C(O)N(R⁹)₂, NHC(O)R⁹, NR⁹C(O)R⁹, NHSO₂R⁹, NHC(O)OR⁹, SO₂NH₂, SO₂NHR⁹, SO₂N(R⁹)₂, NHC(O)NH₂, NHC(O)NHR⁹, OH, (O), C(O)OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br and I;

R⁷, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; R⁸, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

R⁹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

wherein the cyclic moieties represented by R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹ are independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, C(O)C(O)R¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁶SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, CF₃, OCF₃, F, Cl, Br and I;

R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, OR¹³, C(O)OR¹³, OCF₃, CF₃, F, Cl, Br and I;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; and

R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

with the proviso that when X¹ is CR¹ and X² is CR¹; R¹ is hydrogen; Y¹ is NHC(O); Z¹ is

and R² is pyrrolyl; the R² pyrrolyl is not substituted with two alkyl groups. In another embodiment of Formula (IC), Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl. In another embodiment of Formula (IC), Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl. In another embodiment of Formula (IC), Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl; and Y¹ is C(O)NH. In another embodiment of Formula (IC), Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl; and Y¹ is C(O)NH. In another embodiment of Formula (IC), Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl; Y¹ is C(O)NH; and X¹ is N and X² is CR¹. In another embodiment of Formula (IC), Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl; Y¹ is C(O)NH; X¹ is N and X² is CR¹. In another embodiment of Formula (IC), Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl; Y¹ is C(O)NH; X¹ is N and X² is CR¹; wherein R² is phenyl; wherein each R² phenyl is substituted with one substituent independently selected from the group consisting of R⁴, OR⁴, and SO₂R⁴. In another embodiment of Formula (IC), Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl; Y¹ is C(O)NH; X¹ is N and X² is CR¹; wherein R² is phenyl; wherein each R² phenyl is substituted with one substituent independently selected from the group consisting of R⁴, OR⁴, and SO₂R⁴. In another embodiment of Formula (IC), Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl; Y¹ is C(O)NH; X¹ is N and X² is CR¹; wherein R² is phenyl; wherein each R² phenyl is substituted with one substituent independently selected from the group consisting of R⁴, OR⁴, and SO₂R⁴; and R¹, at each occurrence, is hydrogen. In another embodiment of Formula (IC), Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl; Y¹ is C(O)NH; X¹ is N and X² is CR¹; wherein R² is phenyl; wherein each R² phenyl is substituted with one substituent independently selected from the group consisting of R⁴, OR⁴, and SO₂R⁴; and R¹, at each occurrence, is hydrogen. In another embodiment of Formula (IC), Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl; Y¹ is C(O)NH; X¹ is N and X² is CR¹; wherein R² is phenyl; wherein each R² phenyl is substituted with one substituent independently selected from the group consisting of R⁴, OR⁴, and SO₂R⁴; R¹, at each occurrence, is hydrogen; and R⁴, at each occurrence, is heterocyclyl. In another embodiment of Formula (IC), Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl; Y¹ is C(O)NH; X¹ is N and X² is CR¹; wherein R² is phenyl; wherein each R² phenyl is substituted with one substituent independently selected from the group consisting of R⁴, OR⁴, and SO₂R⁴; and R¹, at each occurrence, is hydrogen; and R⁴, at each occurrence, is heterocyclyl.

Still another embodiment pertains to compounds, which are

-   1-(pyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(2-cyanopyridin-3-yl)-N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)-1-[2-(trifluoromethyl)pyridin-3-yl]azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(4-methylpyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(4-fluoropyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)-1-[4-(trifluoromethyl)pyridin-3-yl]azetidine-3-carboxamide; -   tert-butyl     4-[4-({[(3S)-1-(pyridin-3-yl)pyrrolidin-3-yl]carbonyl}amino)phenoxy]piperidine-1-carboxylate; -   tert-butyl     4-[4-({[(3R)-1-(pyridin-3-yl)pyrrolidin-3-yl]carbonyl}amino)phenoxy]piperidine-1-carboxylate; -   1-(pyridin-3-yl)-N-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   (3S)-1-(pyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridin-3-yl)-N-[4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]pyrrolidine-3-carboxamide; -   (3S)-1-(pyridin-3-yl)-N-[4-({1-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]pyrrolidine-3-carboxamide; -   (3S)-1-(pyridin-3-yl)-N-(4-{[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridin-3-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxy}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)pyrrolidine-3-carboxamide; -   N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[1-(pyridin-3-yl)azetidin-3-yl]-4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}benzamide; -   N-(4-{1-[(2S)-2-methylbutanoyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)-N-[1-(pyridin-3-yl)azetidin-3-yl]benzamide; -   4-{[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]oxy}-N-[1-(pyridin-3-yl)azetidin-3-yl]benzamide; -   1-(pyridin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   tert-butyl     4-(4-{[(3S)-1-(pyridin-3-yl)pyrrolidin-3-yl]carbamoyl}phenoxy)piperidine-1-carboxylate; -   tert-butyl     4-(4-{[(3R)-1-(pyridin-3-yl)pyrrolidin-3-yl]carbamoyl}phenoxy)piperidine-1-carboxylate; -   N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-[4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-{4-[(1-pentanoylpiperidin-4-yl)oxy]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-methylpentanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylpentanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-ethoxypropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3,3-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-butanoylpiperidin-4-yl)oxy]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(ethoxyacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(N-acetyl-L-leucyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclohexylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclohexylacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-(4-{[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1-methylcyclohexyl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(furan-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-{4-[(1-acetylpiperidin-4-yl)oxy]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(methoxyacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(morpholin-4-ylacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(furan-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-propanoylpiperidin-4-yl)oxy]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(N,N-dimethyl-beta-alanyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-(4-{[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,3-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(4-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(2-methoxypyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylmethyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpentyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylbutyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-ethylbutyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylpropyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylbutyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-propylpiperidin-4-yl)oxy]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-cyclopropylethyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-(4-{[1-(tetrahydrofuran-3-ylmethyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylbutyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclohexylmethyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopentylmethyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylbutyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylpentyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-butylpiperidin-4-yl)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-ethylbutyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylbutyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylpropyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-propylpiperidin-4-yl)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(4-methoxypyridin-3-yl)azetidine-3-carboxamide; -   1-(4-cyanopyridin-3-yl)-N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-[4-(1-pentanoylpiperidin-4-yl)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(morpholin-4-ylacetyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(furan-3-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-{4-[1-(pyrrolidin-1-ylacetyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(5-oxo-D-prolyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(N,N-dimethyl-beta-alanyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-{4-[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(4-methylpiperazin-1-yl)acetyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(5-oxo-L-prolyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-ethoxypropanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(1-methylcyclohexyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-acetylpiperidin-4-yl)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclohexylacetyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(N-acetyl-L-leucyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-propanoylpiperidin-4-yl)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[3-(morpholin-4-yl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(furan-2-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[3-(piperidin-1-yl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(ethoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-butanoylpiperidin-4-yl)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclohexylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopentylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   (3S)—N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)pyrrolidine-3-carboxamide; -   N-(4-{1-[(2S)-2-methylbutanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,5-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-(4-{1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(pyridazin-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-[4-(1-pentanoylpiperidin-4-yl)phenyl]azetidine-3-carboxamide; -   N-{4-[1-(3-methylpentanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]piperidin-4-yl}phenyl)-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(morpholin-4-ylacetyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(furan-3-ylcarbonyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(pyrrolidin-4-ylacetyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(5-oxo-D-prolyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(N,N-dimethyl-beta-alanyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-(4-{1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(4-methylpiperazin-1-yl)acetyl]piperidin-4-yl}phenyl)-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(5-oxo-L-prolyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(3-ethoxypropanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-methylpentanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(1-methylcyclohexyl)carbonyl]piperidin-4-yl}phenyl)-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-acetylpiperidin-4-yl)phenyl]-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclohexylacetyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(N-acetyl-L-leucyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-[4-(1-propanoylpiperidin-4-yl)phenyl]azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}phenyl)-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-(4-{1-[3-(morpholin-4-yl)propanoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-(4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(furan-2-ylcarbonyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-(4-{1-[3-(piperidin-1-yl)propanoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(ethoxyacetyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-butanoylpiperidin-4-yl)phenyl]-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclohexylcarbonyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-fluorobenzoyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,4-difluorobenzoyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({1-[difluoro(phenyl)acetyl]azetidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({1-[(4,4-difluoro     cyclohexyl)carbonyl]azetidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({1-[(4-fluorophenyl)acetyl]azetidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)pyrrolidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({1-[4-(trifluoromethyl)benzoyl]azetidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-{4-[(1-benzoylazetidin-3-yl)oxy]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-hydroxy-2-methylpropanoyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydrofuran-3-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(furan-3-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[(1-pentanoylazetidin-3-yl)oxy]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[difluoro(phenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methyl-2-phenylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(1,3-thiazol-4-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[(1-{[4-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)oxy]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({1[3-(trifluoromethyl)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({1[3-(trifluoromethoxy)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-(4-{[1-(3-methylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(3-fluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,4-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(4-fluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3,4-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({1-[4-(trifluoromethoxy)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-[4-({1-[(2,4-difluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[(1-{[4-(trifluoromethoxy)phenyl]acetyl}piperidin-4-yl)oxy]phenyl}azetidine-3-carboxamide; -   N-[4-({1-[(3,5-difluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[(1-{[3-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)oxy]phenyl}azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(pyridin-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(3,5-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-acetylpiperidin-4-yl)oxy]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(methoxyacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2-fluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(3-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3,3-dimethylbutanoyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclohexylcarbonyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(2-methylcyclopropyl)carbonyl]azetidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)azetidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylcarbonyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3,3-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclobutylcarbonyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydrofuran-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(4-methylpentanoyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropanoyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2S)-2-methylbutanoyl]azetidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(methoxyacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[difluoro(phenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({1-[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(1,3-thiazol-4-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[(1-{[4-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)oxy]phenyl}azetidine-3-carboxamide; -   N-(4-{[1-(3,4-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[(1-{[4-(trifluoromethoxy)phenyl]acetyl}piperidin-4-yl)oxy]phenyl}azetidine-3-carboxamide; -   N-[4-({1-[(4-fluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2,4-difluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(2-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methyl-2-phenylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[(1-acetylpiperidin-4-yl)oxy]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(2,4-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({1[3-(trifluoromethyl)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-(4-{[1-(3-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-[4-({1-[(3-fluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({1-[4-(trifluoromethoxy)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-[4-({1-[(3,5-difluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({1[3-(trifluoromethoxy)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(pyridin-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(4-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(3,5-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[(1-{[3-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)oxy]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2-fluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]furan-2-carboxamide; -   (3S)—N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   tert-butyl     4-(4-{[1-(pyridazin-3-yl)azetidin-3-yl]carbamoyl}phenyl)piperidine-1-carboxylate; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   N-[4-(1-acetylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-butanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-pentanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-hexanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-ethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-heptanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(but-3-enoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(p     ent-4-enoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(methylsulfanyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-nitropropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[3-(methylsulfanyl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(pent-4-ynoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclohexylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclohexylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-hydroxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-hydroxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-hydroxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methoxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methoxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-methoxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-cyanobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-cyanobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{1-[3-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{1-[3-(trifluoromethoxy)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(2,3-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,4-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,5-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,4-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,5-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,4-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,5-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,4-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,5-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(3-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(4-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2-chlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(4-chlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-(1-{[4-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)phenyl]azetidine-3-carboxamide; -   N-(4-{1-[(3,5-dimethylphenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2,5-difluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(3,4-dichlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(furan-3-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(5-methylpyrazin-2-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-ethoxypropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(1-phenylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{1-[(pyrimidin-2-ylsulfanyl)acetyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-(4-{1-[(1-acetylpiperidin-4-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(3,5-difluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(N-acetyl-L-leucyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(diphenylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-fluoro-2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(5-fluoro-2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-fluoro-4-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,3-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[4-(propan-2-yl)benzoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-tert-butylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[2-fluoro-5-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[2-chloro-5-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(4-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(4-methylphenoxy)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2S)-2-phenylbutanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-(1-{[3-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)phenyl]azetidine-3-carboxamide; -   N-(4-{1-[(3-chlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2,4-dichlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(naphthalen-1-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2R)-2-methoxy-2-phenylacetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[N-(furan-2-ylcarbonyl)glycyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(benzyloxy)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(naphthalen-1-ylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(N-benzoylglycyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{1-[4-(thiophen-2-yl)butanoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(2,5-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclobutylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-{N-[(4-methylphenyl)sulfonyl]glycyl}piperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2,3-difluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2S)-2-methoxy-2-phenylacetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(naphthalen-2-ylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-phenylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2,6-dichlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[3-(phenylsulfonyl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(2,5-dimethylfuran-3-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(1,3-thiazol-4-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(1,3-thiazol-5-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(ethoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(6-methylpyridin-3-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(furan-2-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(1-methylcyclohexyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-oxopropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopentylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-propanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(1,3-thiazol-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(tetrahydro-2H-pyran-4-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-{[4-(trifluoromethoxy)phenyl]acetyl}pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(thiophen-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(4-fluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(3,5-difluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(3-fluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({(3R)-1-[3-(trifluoromethyl)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(2,4-difluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-{[4-(trifluoromethyl)phenyl]acetyl}pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(1,3-thiazol-4-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(tetrahydrofuran-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(5-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(2-fluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({(3R)-1-[3-(trifluoromethoxy)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(pyridin-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(4-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-methyl-2-phenylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(methoxyacetyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(thiophen-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-{[3-(trifluoromethyl)phenyl]acetyl}pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2,2-dimethylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({(3R)-1-[4-(trifluoromethyl)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({(3R)-1-[4-(trifluoromethoxy)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3-methylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[difluoro(phenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide;     N-[4-({(3R)-1-[(4,4-difluorocyclohexyl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(1,3-thiazol-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(tetrahydro-2H-pyran-4-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-{[4-(trifluoromethoxy)phenyl]acetyl}pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(4-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(thiophen-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(4-fluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(3,5-difluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(3-fluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({(3R)-1-[3-(trifluoromethyl)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(2,4-difluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-{[4-(trifluoromethyl)phenyl]acetyl}pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(1,3-thiazol-4-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(tetrahydrofuran-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(5-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(2-fluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({(3R)-1-[3-(trifluoromethoxy)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(pyridin-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(4-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-methyl-2-phenylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(methoxyacetyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(thiophen-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-{[3-(trifluoromethyl)phenyl]acetyl}pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2,2-dimethylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({(3R)-1-[4-(trifluoromethyl)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({(3R)-1-[4-(trifluoromethoxy)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3-methylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[difluoro(phenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1[(4,4-difluorocyclohexyl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(4-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{1-[(3,5-difluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,4-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{1-[(3-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{1-[3-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-(4-{1-[(2,4-difluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(1,3-thiazol-4-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(pyridin-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(3-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methyl-2-phenylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-(1-{[3-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)phenyl]azetidine-3-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{1-[4-(trifluoromethoxy)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[difluoro(phenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{1-[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-(1-{[4-(trifluoromethoxy)phenyl]acetyl}piperidin-4-yl)phenyl]azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{1-[3-(trifluoromethoxy)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-(1-{[4-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)phenyl]azetidine-3-carboxamide; -   N-(4-{[1-(3-chlorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-tert-butylbenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-methoxybenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-methylbenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclohexylcarbonyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methoxybenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2S)-2-phenylbutanoyl]piperidin-4-yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[4-(propan-2-yl)benzoyl]piperidin-4-yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-chlorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-benzoylpiperidin-4-yl)sulfonyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]sulfonyl}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(2,5-difluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylbenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(4-fluorophenyl)acetyl]piperidin-4-yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylbenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,3-dimethylbenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(3-fluorophenyl)acetyl]piperidin-4-yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-fluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({1[3-(trifluoromethyl)benzoyl]piperidin-4-yl}sulfonyl)phenyl]azetidine-3-carboxamide; -   N-[4-({1-[(3,5-difluorophenyl)acetyl]piperidin-4-yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,4-difluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}sulfonyl)phenyl]azetidine-3-carboxamide; -   N-(4-{[1-(4-fluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,3-difluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,4-dichlorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(naphthalen-1-ylcarbonyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylcarbonyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3,5-difluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3,3-dimethylbutanoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methoxybenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylbutanoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylcarbonyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(phenylacetyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1-phenylcyclopropyl)carbonyl]piperidin-4-yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylalanyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3R)-1-(pyridin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3R)-1-(pyridazin-4-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3R)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3S)-1-(pyridazin-4-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3S)-1-(pyridin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   tert-butyl     4-(2-methyl-1-oxo-1-{4-[4-({[1-(pyridin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]piperidin-1-yl}propan-2-yl)piperazine-1-carboxylate; -   N-(4-{1[2-methyl-2-(piperazin-1-yl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-chlorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-methylpentanoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2-fluorophenyl)acetyl]piperidin-4-yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[(1-benzoylpiperidin-4-yl)sulfonyl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-fluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylcarbonyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[(3R)-1-(5,6-dichloropyridazin-4-yl)pyrrolidin-3-yl]-5[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide; -   N-[(3R)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide; -   N-[(3S)-1-(5,6-dichloropyridazin-4-yl)pyrrolidin-3-yl]-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide; -   N-[(3S)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]-5[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide; -   N-[(3R)-1-(5,6-dichloropyridazin-4-yl)pyrrolidin-3-yl]-5[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-3-carboxamide; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3R)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-3-carboxamide; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3R)-1-(pyridazin-4-yl)pyrrolidin-3-yl]thiophene-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)piperidine-4-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)piperidine-4-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)piperidine-4-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}piperidine-4-carboxamide; -   N-[(3S)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]-5[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(1,3-thiazol-5-ylcarbonyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2S)-2-phenylbutanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2S)-2-methoxy-2-phenylacetyl]piperidin-4-yl}     phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2R)-2-methoxy-2-phenylacetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(ethoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(4-methylphenoxy)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(naphthalen-1-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2,6-dichlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(naphthalen-1-ylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-(4-{1-[4-(thiophen-2-yl)butanoyl]piperidin-4-yl}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,5-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(naphthalen-2-ylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[3-(phenylsulfonyl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-[4-(1-{[3-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)phenyl]pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(furan-2-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(N-benzoylglycyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2,4-dichlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(1-methylcyclohexyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(6-methylpyridin-3-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(3-chlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-propanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclopentylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclopropylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-fluoro-5-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(5-fluoropyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(2-fluoro-6-methylpyridin-3-yl)azetidine-3-carboxamide; -   (3S)—N-{4-[1-(2-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,4-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-heptanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,4-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(4-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,3-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-hexanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-butanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(3,5-dimethylphenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3,5-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-fluoro-2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(4-chlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(furan-3-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3,4-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[2-chloro-5-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-acetylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3,5-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-ethoxypropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,5-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,5-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(5-fluoro-2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(diphenylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-(4-{1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(pent-4-enoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-(4-{1-[3-(trifluoromethoxy)benzoyl]piperidin-4-yl}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(1-phenylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[2-fluoro-5-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclohexylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-methoxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-ethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-tert-butylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-(4-{1-[3-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(pent-4-ynoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(3-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[3-(methylsulfanyl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(1-acetylpiperidin-4-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(but-3-enoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-fluoro-4-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-methoxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2-chlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(N-acetyl-L-leucyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-cyanobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-methoxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,3-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[4-(propan-2-yl)benzoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclohexylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-hydroxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-cyanobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(2-cyanopyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(4-cyanopyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-fluoro-4-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(5-cyanopyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(5-methylpyridin-3-yl)azetidine-3-carboxamide; -   2-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]-1,3-thiazole-5-carboxamide; -   (3S)—N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(2-methylpyridin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(2-methylpyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   N-[(3S)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]furan-2-carboxamide; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]furan-2-carboxamide; -   N-(4-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[(3S)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]-4-[1-(2-methylpropanoyl)piperidin-4-yl]benzamide; -   N-(4-{1-[2-(piperazin-1-yl)ethyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   4-[1-(2-methylpropanoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]benzamide; -   N-{4-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   5-[1-(3-fluorobenzoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-[1-(4-fluorobenzoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   (3S)—N-(4-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]-5[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]thiophene-2-carboxamide; -   (3S)—N-{4-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   5-[1-(2-methylpropanoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-{1[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-(1-benzoylpiperidin-4-yl)-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]-5[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]thiophene-2-carboxamide; -   N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]-5-{1[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}thiophene-2-carboxamide; -   5-{1-[(1-methylpiperidin-4-yl)acetyl]piperidin-4-yl}-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]-5-[1-(1,3-thiazol-4-ylcarbonyl)piperidin-4-yl]thiophene-2-carboxamide; -   (3S)—N-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(propan-2-yl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclopropylmethyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-2-ylmethyl)-1H-pyrazol-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-tert-butyl-1H-pyrazol-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-benzoylpyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-(2-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-(3-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-(4-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-(2-methylbenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-({(3R)-1-[(4,4-difluorocyclohexyl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(4,4,4-trifluorobutanoyl)pyrrolidin-3-yl]oxy}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-[4-(5-propyl-1,2,4-oxadiazol-3-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   (3S)—N-{4-[1-(2-fluorobenzoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-fluorobenzoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-fluorobenzoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-benzoylazetidin-3-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,2-dimethylpropanoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3,5-difluorobenzoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-methylbenzoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,4-difluorobenzoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3R)—N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3R)—N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3R)—N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(cyclohexylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(3-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[(1-benzoylpiperidin-4-yl)oxy]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(4-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-({1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-{4-[5-(2,2-dimethylpropyl)-1,3,4-oxadiazol-2-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropyl)-1H-imidazol-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[5-(2,2-dimethylpropyl)-1,2,4-oxadiazol-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[3-cyclopropyl-1-(2-methoxyethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   tert-butyl     4-(5-{[1-(pyridazin-3-yl)azetidin-3-yl]carbamoyl}thiophen-2-yl)piperidine-1-carboxylate; -   tert-butyl     4-fluoro-4-[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]piperidine-1-carboxylate; -   5-(1-benzoylpiperidin-4-yl)-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2-methylbenzoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   5-[1-(3-fluorobenzoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   5-[1-(4-fluorobenzoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   5-[1-(3,5-difluorobenzoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   N-{4-[3-cyclopropyl-1-(2-hydroxyethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   1-(6-fluoropyridazin-3-yl)-N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(2-ethylbutanoyl)piperidin-4-yl]phenyl}-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   (3S)—N-(4-{[(3S)-1-benzoylpyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3S)-1-(2-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3S)-1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3S)-1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-{2-fluoro-4[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)-2-fluorophenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   (3S)—N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[(1-benzoylpiperidin-4-yl)oxy]phenyl}-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(cyclohexylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-{4-[8-(2-methylpropanoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4[8-(4,4,4-trifluorobutanoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}azetidine-3-carboxamide; -   N-[4-(8-benzoyl-8-azabicyclo[3.2.1]oct-3-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[8-(2-fluorobenzoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[8-(2,2-dimethylpropanoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{8-[(1-methylcyclopropyl)carbonyl]-8-azabicyclo[3.2.1]oct-3-yl}     phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methoxyethyl)-3-(2-methylpropyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   5-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   5-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   N-[1-(pyridazin-3-yl)azetidin-3-yl]-5-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]thiophene-2-carboxamide; -   5-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   benzyl     4-[4-({[1-(6-chloropyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-4-fluoropiperidine-1-carboxylate; -   benzyl     4-[4-({[1-(6-chloropyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-4-hydroxypiperidine-1-carboxylate; -   N-[1-(pyridazin-3-yl)azetidin-3-yl]-5-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]thiophene-2-carboxamide; -   5-[1-(cyclopropylcarbonyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   N-{4-[4-fluoro-1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylcarbonyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(2-fluoro-4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoyl-4-fluoropiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)-4-fluoropiperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4[3-tert-butyl-1-(2-methoxyethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-butyl-3-tert-butyl-1H-pyrazol-5-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[3-tert-butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)-2-fluorophenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{1-[(4-methylpiperidin-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(6-chloropyridazin-3-yl)-N-{4-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]phenyl}azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(4-methylpiperidin-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-{3-fluoro-4[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{3-fluoro-4[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{3-fluoro-4[1-(3,3,3-tri     fluoropropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-3-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{3-fluoro-4[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)-3-fluorophenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{3-fluoro-4[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-3-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{3-fluoro-4[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]-3-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)-4-hydroxypiperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)-4-hydroxypiperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(6-methylpyridazin-3-yl)-N-(4-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)azetidine-3-carboxamide; -   (3S)—N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-{4-[(1-benzoylpiperidin-4-yl)methyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3,3-dimethylbutanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-ethylbutanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-acetylpiperidin-4-yl)methyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-{[4-methyl-1-(oxetan-3-yl)piperidin-4-yl]methyl}-1H-pyrazol-4-yl)phenyl]-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(4-methylpyridazin-3-yl)azetidine-3-carboxamide; -   5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]furan-2-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(3-methylpyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(3-methylpyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2-aminopyridin-3-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-methyl-5-[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-1H-pyrazole-3-carboxylic     acid; -   ethyl     1-methyl-5-[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-1H-pyrazole-3-carboxylate; -   ethyl     1-phenyl-5[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-1H-pyrazole-3-carboxylate; -   N-{6[1-(2-fluorobenzoyl)piperidin-4-yl]pyridin-3-yl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3-methylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   1-(6-methylpyridazin-3-yl)-N-(4-{[(3R)-1-(1,3-thiazol-4-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{6[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]pyridin-3-yl}azetidine-3-carboxamide; -   N-{6-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]pyridin-3-yl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   (3S)—N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(4-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(4-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-{4-[1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{6-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]pyridin-3-yl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   tert-butyl     4-[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)-1H-pyrazol-1-yl]piperidine-1-carboxylate; -   N-(6-{1-[(4-methylpiperidin-4-yl)methyl]-1H-pyrazol-4-yl}pyridin-3-yl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(1,3-thiazol-5-ylcarbonyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(1H-pyrazol-4-ylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylbutanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-{1-[(methylsulfanyl)acetyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpentanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-methylpentanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[3-(methylsulfanyl)propanoyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(1,3-thiazol-4-ylcarbonyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(1H-pyrazol-5-ylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(6-methylpyridin-3-yl)carbonyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(pent-4-ynoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(methoxyacetyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(ethoxyacetyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-{4-[(1-hexanoylpiperidin-4-yl)methyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(but-3-enoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(furan-2-ylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(1,2-oxazol-5-ylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(pyridin-2-ylcarbonyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(furan-3-ylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylbutanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-propanoylpiperidin-4-yl)methyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-butanoylpiperidin-4-yl)methyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclobutylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-pentanoylpiperidin-4-yl)methyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylacetyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylbenzoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylpentanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclohexylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylbutanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(4-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-{1-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-1H-pyrazol-4-yl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{1-[1-(2-fluorobenzoyl)piperidin-4-yl]-1H-pyrazol-4-yl}-1-(pyridazin-3-yl)azetidine-3-carboxamide;

N-[4-(phenylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide;

-   N-{4[(2,2-dimethylpropyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(3-methoxy-2,2-dimethylpropyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4[(2-cyclopropylethyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[2-(2-ethylpiperidin-1-yl)ethyl]carbamoyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(cyclobutylmethyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(2S)-butan-2-ylcarbarnoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(butylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(2,2-dimethyltetrahydro-2H-pyran-4-yl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(1S)-1-cyclopropylethyl]carbamoyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({2-[methyl(phenyl)amino]ethyl}carbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1,1′-bi(cyclopropyl)-1-ylcarbarnoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-(thiophen-3-ylcarbamoyl)phenyl]azetidine-3-carboxamide; -   N-(4-{[(1R)-1-cyclopropylethyl]carbamoyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-methylpiperidin-4-yl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4[(2R)-butan-2-ylcarbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-azabicyclo[2.2.2]oct-3-ylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl}azetidine-3-carboxamide; -   N-{4-[(oxetan-3-ylmethyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(2-methylcyclopropyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(cyclobutylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-methylcyclopropyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(2-methoxy-2-methylpropyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(cyclopropylmethyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4[(3,3,3-trifluoropropyl)carbamoyl]phenyl}azetidine-3-carboxamide; -   N-{4[(1-methylpiperidin-3-yl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3-methyloxetan-3-yl)methyl]carbamoyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-(tetrahydro-2H-pyran-4-ylcarbamoyl)phenyl]azetidine-3-carboxamide; -   N-(4-{[(1-methylpiperidin-3-yl)methyl]carbamoyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(cyclopropylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(cyclopentylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(benzylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(3-fluorophenyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(propylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(4-fluorophenyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(2-fluorophenyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-methylcyclobutyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(prop-2-en-1-ylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   5-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]-5-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]thiophene-2-carboxamide; -   5-[1-(cyclopropylacetyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-[1-(bicyclo[2.2.1]hept-2-ylacetyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[(3S)-tetrahydrofuran-3-ylcarbamoyl]phenyl}azetidine-3-carboxamide; -   N-[4-({4-[2-(dimethylamino)ethyl]phenyl}carbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl}azetidine-3-carboxamide; -   N-{4-[(2-methoxy     ethyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-amino-2,2-dimethylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[2,2-dimethyl-3-(piperazin-1-yl)propyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1[2-methyl-2-(piperazin-1-yl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide;     and pharmaceutically acceptable salts thereof

Still another embodiment pertains to compounds of Formula (1A), selected from the group consisting of

-   N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   (3S)—N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-[4-(1-acetylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-butanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(methylsulfanyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-[4-(1-propanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   (3S)—N-[4-(1-propanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-butanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-acetylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-ethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3R)—N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide;     and pharmaceutically acceptable salts thereof.

Another embodiment pertains to a composition for treating inflammatory and tissue repair disorders; particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic upus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, particularly wherein the cancer is selected from breast, prostate, lung, colon, cervix, ovary, skin, CNS, bladder, pancreas, leukemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia, said composition comprising an excipient and a therapeutically effective amount of a compound of Formula (IC), or pharmaceutically acceptable salts thereof.

Another embodiment pertains to a method of treating inflammatory and tissue repair disorders; particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, particularly wherein the cancer is selected from breast, prostate, lung, colon, cervix, ovary, skin, CNS, bladder, pancreas, leukemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia in a patient, said method comprising administering to the patient a therapeutically effective amount of a compound of Formula (IC), or pharmaceutically acceptable salts thereof.

Another embodiment pertains to a method of treating inflammatory and tissue repair disorders; particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, particularly wherein the cancer is selected from breast, prostate, lung, colon, cervix, ovary, skin, CNS, bladder, pancreas, leukemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia or spleen cancer in a patient, said method comprising administering to the patient therapeutically effective amount of the compound of Formula (IC), or pharmaceutically acceptable salts thereof; and a therapeutically effective amount of one additional therapeutic agent or more than one additional therapeutic agent.

DETAILED DESCRIPTION OF THE INVENTION

This detailed description is intended only to acquaint others skilled in the art with Applicants' invention, its principles, and its practical application so that others skilled in the art may adapt and apply the invention in its numerous forms, as they may be best suited to the requirements of a particular use. This description and its specific examples are intended for purposes of illustration only. This invention, therefore, is not limited to the embodiments described in this patent application, and may be variously modified.

ABBREVIATIONS AND DEFINITIONS

Unless otherwise defined herein, scientific and technical terms used in connection with the present invention shall have the meanings that are commonly understood by those of ordinary skill in the art. The meaning and scope of the terms should be clear, however, in the event of any latent ambiguity, definitions provided herein take precedent over any dictionary or extrinsic definition. In this application, the use of “or” means “and/or” unless stated otherwise. Furthermore, the use of the term “including”, as well as other forms, such as “includes” and “included”, is not limiting. With reference to the use of the words “comprise” or “comprises” or “comprising” in this patent application (including the claims), Applicants note that unless the context requires otherwise, those words are used on the basis and clear understanding that they are to be interpreted inclusively, rather than exclusively, and that Applicants intend each of those words to be so interpreted in construing this patent application, including the claims below. For a variable that occurs more than one time in any substituent or in the compound of the invention or any other formulae herein, its definition on each occurrence is independent of its definition at every other occurrence. Combinations of substituents are permissible only if such combinations result in stable compounds. Stable compounds are compounds which can be isolated in a useful degree of purity from a reaction mixture.

It is meant to be understood that proper valences are maintained for all combinations herein, that monovalent moieties having more than one atom are attached through their left ends, and that divalent moieties are drawn from left to right.

As used in the specification and the appended claims, unless specified to the contrary, the following terms have the meaning indicated:

The term “alkyl” (alone or in combination with another term(s)) means a straight-or branched-chain saturated hydrocarbyl substituent typically containing from 1 to about 10 carbon atoms; or in another embodiment, from 1 to about 8 carbon atoms; in another embodiment, from 1 to about 6 carbon atoms; and in another embodiment, from 1 to about 4 carbon atoms. Examples of such substituents include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, iso-amyl, and hexyl and the like.

The term “alkenyl” (alone or in combination with another term(s)) means a straight-or branched-chain hydrocarbyl substituent containing one or more double bonds and typically from 2 to about 10 carbon atoms; or in another embodiment, from 2 to about 8 carbon atoms; in another embodiment, from 2 to about 6 carbon atoms; and in another embodiment, from 2 to about 4 carbon atoms. Examples of such substituents include ethenyl (vinyl), 2-propenyl, 3-propenyl, 1,4-pentadienyl, 1,4-butadienyl, 1-butenyl, 2-butenyl, and 3-butenyl and the like.

The term “alkynyl” (alone or in combination with another term(s)) means a straight-or branched-chain hydrocarbyl substituent containing one or more triple bonds and typically from 2 to about 10 carbon atoms; or in another embodiment, from 2 to about 8 carbon atoms; in another embodiment, from 2 to about 6 carbon atoms; and in another embodiment, from 2 to about 4 carbon atoms. Examples of such substituents include ethynyl, 2-propynyl, 3-propynyl, 2-butynyl, and 3-butynyl and the like.

The term “carbocyclyl” (alone or in combination with another term(s)) means a saturated cyclic (i.e., “cycloalkyl”), partially saturated cyclic (i.e., “cycloalkenyl”), or completely unsaturated (i.e., “aryl”) hydrocarbyl substituent containing from 3 to 14 carbon ring atoms (“ring atoms” are the atoms bound together to form the ring or rings of a cyclic substituent). A carbocyclyl may be a single-ring (monocyclic) or polycyclic ring structure.

A carbocyclyl may be a single ring structure, which typically contains from 3 to 8 ring atoms, more typically from 3 to 6 ring atoms, and even more typically 5 to 6 ring atoms. Examples of such single-ring carbocyclyls include cyclopropyl (cyclopropanyl), cyclobutyl (cyclobutanyl), cyclopentyl (cyclopentanyl), cyclopentenyl, cyclopentadienyl, cyclohexyl (cyclohexanyl), cyclohexenyl, cyclohexadienyl, and phenyl. A carbocyclyl may alternatively be polycyclic (i.e., may contain more than one ring). Examples of polycyclic carbocyclyls include bridged, fused, and spirocyclic carbocyclyls. In a spirocyclic carbocyclyl, one atom is common to two different rings. An example of a spirocyclic carbocyclyl is spiropentanyl. In a bridged carbocyclyl, the rings share at least two common non-adjacent atoms. Examples of bridged carbocyclyls include bicyclo[2.2.1]heptanyl, bicyclo[2.2.1]hept-2-enyl, and adamantanyl. In a fused-ring carbocyclyl system, two or more rings may be fused together, such that two rings share one common bond. Examples of two- or three-fused ring carbocyclyls include naphthalenyl, tetrahydronaphthalenyl (tetralinyl), indenyl, indanyl (dihydroindenyl), anthracenyl, phenanthrenyl, and decalinyl.

The term “cycloalkyl” (alone or in combination with another term(s)) means a saturated cyclic hydrocarbyl substituent containing from 3 to 14 carbon ring atoms. A cycloalkyl may be a single carbon ring, which typically contains from 3 to 8 carbon ring atoms and more typically from 3 to 6 ring atoms. Examples of single-ring cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. A cycloalkyl may alternatively be polycyclic or contain more than one ring. Examples of polycyclic cycloalkyls include bridged, fused, and spirocyclic carbocyclyls.

The term “aryl” (alone or in combination with another term(s)) means an aromatic carbocyclyl containing from 6 to 14 carbon ring atoms. An aryl may be monocyclic or polycyclic (i.e., may contain more than one ring). In the case of polycyclic aromatic rings, only one ring the polycyclic system is required to be unsaturated while the remaining ring(s) may be saturated, partially saturated or unsaturated. Examples of aryls include phenyl, naphthalenyl, indenyl, indanyl, and tetrahydronapthyl.

In some instances, the number of carbon atoms in a hydrocarbyl substituent (e.g., alkyl, alkenyl, alkynyl, or cycloalkyl) is indicated by the prefix “C_(x)-C_(y)-”, wherein x is the minimum and y is the maximum number of carbon atoms in the substituent. Thus, for example, “C₁-C₆-alkyl” refers to an alkyl substituent containing from 1 to 6 carbon atoms. Illustrating further, C₃-C₈-cycloalkyl means a saturated hydrocarbyl ring containing from 3 to 8 carbon ring atoms.

The term “hydrogen” (alone or in combination with another term(s)) means a hydrogen radical, and may be depicted as —H.

The term “hydroxy” (alone or in combination with another term(s)) means —OH.

The term “carboxy” (alone or in combination with another term(s)) means —C(O)—OH.

The term “amino” (alone or in combination with another term(s)) means —NH₂.

The term “halogen” or “halo” (alone or in combination with another term(s)) means a fluorine radical (which may be depicted as —F), chlorine radical (which may be depicted as —Cl), bromine radical (which may be depicted as —Br), or iodine radical (which may be depicted as —I).

If a substituent is described as being “substituted”, a non-hydrogen radical is in the place of hydrogen radical on a carbon or nitrogen of the substituent. Thus, for example, a substituted alkyl substituent is an alkyl substituent in which at least one non-hydrogen radical is in the place of a hydrogen radical on the alkyl substituent. To illustrate, monofluoroalkyl is alkyl substituted with a fluoro radical, and difluoroalkyl is alkyl substituted with two fluoro radicals. It should be recognized that if there are more than one substitution on a substituent, each non-hydrogen radical may be identical or different (unless otherwise stated).

If a substituent is described as being “optionally substituted”, the substituent may be either (1) not substituted or (2) substituted. If a substituent is described as being optionally substituted with up to a particular number of non-hydrogen radicals, that substituent may be either (1) not substituted; or (2) substituted by up to that particular number of non-hydrogen radicals or by up to the maximum number of substitutable positions on the substituent, whichever is less. Thus, for example, if a substituent is described as a heteroaryl optionally substituted with up to 3 non-hydrogen radicals, then any heteroaryl with less than 3 substitutable positions would be optionally substituted by up to only as many non-hydrogen radicals as the heteroaryl has substitutable positions. To illustrate, tetrazolyl (which has only one substitutable position) would be optionally substituted with up to one non-hydrogen radical. To illustrate further, if an amino nitrogen is described as being optionally substituted with up to 2 non-hydrogen radicals, then a primary amino nitrogen will be optionally substituted with up to 2 non-hydrogen radicals, whereas a secondary amino nitrogen will be optionally substituted with up to only 1 non-hydrogen radical. If a substituent is described as being optionally substituted with one or more non-hydrogen radicals, that substituent may be either (1) not substituted; or (2) substituted by up to the maximum number of substitutable positions on the substituent. Thus, for example, if a substituent is described as a heteroaryl optionally substituted with one or more non-hydrogen radicals, then any heteroaryl with 3 substitutable positions would be optionally substituted by one, two or three non-hydrogen radicals. To illustrate, tetrazolyl (which has only one substitutable position) would be optionally substituted with up to one non-hydrogen radical.

This patent application uses the terms “substituent” and “radical” interchangeably.

The prefix “halo” indicates that the substituent to which the prefix is attached is substituted with one or more independently selected halogen radicals. For example, haloalkyl means an alkyl substituent in which at least one hydrogen radical is replaced with a halogen radical. Examples of haloalkyls include chloromethyl, 1-bromoethyl, fluoromethyl, difluoromethyl, trifluoromethyl, and 1,1,1-trifluoroethyl. It should be recognized that if a substituent is substituted by more than one halogen radical, those halogen radicals may be identical or different (unless otherwise stated).

The prefix “perhalo” indicates that every hydrogen radical on the substituent to which the prefix is attached is replaced with independently selected halogen radicals, i.e., each hydrogen radical on the substituent is replaced with a halogen radical. If all the halogen radicals are identical, the prefix typically will identify the halogen radical. Thus, for example, the term “perfluoro” means that every hydrogen radical on the substituent to which the prefix is attached is substituted with a fluorine radical. To illustrate, the term “perfluoroalkyl” means an alkyl substituent wherein a fluorine radical is in the place of each hydrogen radical.

The term “carbonyl” (alone or in combination with another term(s)) means —C(O)—.

The term “aminocarbonyl” (alone or in combination with another term(s)) means —C(O)—NH₂.

The term “oxo” (alone or in combination with another term(s)) means (═O).

The term “oxy” (alone or in combination with another term(s)) means an ether substituent, and may be depicted as —O—.

The term “alkylhydroxy” (alone or in combination with another term(s)) means alkyl-OH.

The term “alkylamino” (alone or in combination with another term(s)) means alkyl-NH₂.

The term “alkyloxy” (alone or in combination with another term(s)) means an alkylether substituent, i.e., —O-alkyl. Examples of such a substituent include methoxy (—O—CH₃), ethoxy, n-propoxy, isopropoxy, n-butoxy, iso-butoxy, sec-butoxy, and tert-butoxy.

The term “alkylcarbonyl” (alone or in combination with another term(s)) means —C(O)-alkyl.

The term “aminoalkylcarbonyl” (alone or in combination with another term(s)) means —C(O)-alkyl-NH₂.

The term “alkyloxycarbonyl” (alone or in combination with another term(s)) means —C(O)—O-alkyl.

The term “carbocyclylcarbonyl” (alone or in combination with another term(s)) means —C(O)-carbocyclyl.

Similarly, the term “heterocyclylcarbonyl” (alone or in combination with another term(s)) means —C(O)-heterocyclyl.

The term “carbocyclylalkylcarbonyl” (alone or in combination with another term(s)) means —C(O)-alkyl-carbocyclyl.

Similarly, the term “heterocyclylalkylcarbonyl” (alone or in combination with another term(s)) means —C(O)-alkyl-heterocyclyl.

The term “carbocyclyloxycarbonyl” (alone or in combination with another term(s)) means —C(O)—O-carbocyclyl.

The term “carbocyclylalkyloxycarbonyl” (alone or in combination with another term(s)) means —C(O)—O-alkyl-carbocyclyl.

The term “thio” or “thia” (alone or in combination with another term(s)) means a thiaether substituent, i.e., an ether substituent wherein a divalent sulfur atom is in the place of the ether oxygen atom. Such a substituent may be depicted as —S—. This, for example, “alkyl-thio-alkyl” means alkyl-S-alkyl (alkyl-sulfanyl-alkyl).

The term “thiol” or “sulfhydryl” (alone or in combination with another term(s)) means a sulfhydryl substituent, and may be depicted as —SH.

The term “(thiocarbonyl)” (alone or in combination with another term(s)) means a carbonyl wherein the oxygen atom has been replaced with a sulfur. Such a substituent may be depicted as —C(S)—.

The term “sulfonyl” (alone or in combination with another term(s)) means —S(O)₂—.

The term “aminosulfonyl” (alone or in combination with another term(s)) means —S(O)₂—NH₂.

The term “sulfinyl” or “sulfoxido” (alone or in combination with another term(s)) means —S(O)—.

The term “heterocyclyl” (alone or in combination with another term(s)) means a saturated (i.e., “heterocycloalkyl”), partially saturated (i.e., “heterocycloalkenyl”), or completely unsaturated (i.e., “heteroaryl”) ring structure containing a total of 3 to 14 ring atoms. At least one of the ring atoms is a heteroatom (i.e., oxygen, nitrogen, or sulfur), with the remaining ring atoms being independently selected from the group consisting of carbon, oxygen, nitrogen, and sulfur. A heterocyclyl may be a single-ring (monocyclic) or polycyclic ring structure.

A heterocyclyl may be a single ring, which typically contains from 3 to 7 ring atoms, more typically from 3 to 6 ring atoms, and even more typically 5 to 6 ring atoms. Examples of single-ring heterocyclyls include 1,2,3,6-tetrahydropyridine, thiomorpholinyl, tetrahydropyranyl, furanyl, dihydrofuranyl, tetrahydrofuranyl, thiophenyl (thiofuranyl), dihydrothiophenyl, tetrahydrothiophenyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, triazolyl, tetrazolyl, oxazolyl, oxazolidinyl, isoxazolidinyl, isoxazolyl, thiazolyl, isothiazolyl, thiazolinyl, isothiazolinyl, thiazolidinyl, isothiazolidinyl, thiodiazolyl, oxadiazolyl (including 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl (furazanyl), or 1,3,4-oxadiazolyl), oxatriazolyl (including 1,2,3,4-oxatriazolyl or 1,2,3,5-oxatriazolyl), dioxazolyl (including 1,2,3-dioxazolyl, 1,2,4-dioxazolyl, 1,3,2-dioxazolyl, or 1,3,4-dioxazolyl), oxathiazolyl, oxathiolyl, oxathiolanyl, pyranyl, dihydropyranyl, thiopyranyl, tetrahydrothiopyranyl, pyridinyl (azinyl), piperidinyl, diazinyl (including pyridazinyl (1,2-diazinyl), pyrimidinyl (1,3-diazinyl), or pyrazinyl (1,4-diazinyl)), piperazinyl, pyrrolidin-2-only, triazinyl (including 1,3,5-triazinyl, 1,2,4-triazinyl, and 1,2,3-triazinyl)), oxazinyl (including 1,2-oxazinyl, 1,3-oxazinyl, or 1,4-oxazinyl)), oxathiazinyl (including 1,2,3-oxathiazinyl, 1,2,4-oxathiazinyl, 1,2,5-oxathiazinyl, or 1,2,6-oxathiazinyl)), oxadiazinyl (including 1,2,3-oxadiazinyl, 1,2,4-oxadiazinyl, 1,4,2-oxadiazinyl, or 1,3,5-oxadiazinyl)), morpholinyl, azepinyl, oxepinyl, thiepinyl, and diazepinyl.

A heterocyclyl may alternatively be polycyclic (i.e., may contain more than one ring). Examples of polycyclic heterocyclyls include bridged, fused, and spirocyclic heterocyclyls. In a spirocyclic heterocyclyl, one atom is common to two different rings. In a bridged heterocyclyl, the rings share at least two common non-adjacent atoms. In a fused-ring heterocyclyl, two or more rings may be fused together, such that two rings share one common bond. Examples of fused-ring heterocyclyls include hexahydro-furo[3,4-c]pyrrole, hexahydro-furo[3,4-b]pyrrole, octahydro-pyrrolo[3,4-b]pyridine, octahydro-pyrrolo[3,4-c]pyridine, (3aR,6aR)-5-methyl-octahydro-pyrrolo[3,4-b]pyrrole, (3aR,6aR)-octahydro-pyrrolo[3,4-b]pyrrole, 6-methyl-2,6-diaza-bicyclo[3.2.0]heptane, (3aS,6aR)-2-methyl-octahydro-pyrrolo[3,4-c]pyrrole, decahydro-[1,5]naphthyridine, 2,3-dihydrobenzofuranyl, 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indolyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, phthalazin-1(2H)-onyl, isoquinolinyl, isoquinolin-1(2H)-onyl, 5,6,7,8-tetrahydrophthalazin-1(2H)-onyl, fluorophthalazin-1(2H)-onyl, (Z)-3H-benzo[d][1,2]diazepin-4(5H)-onyl, (trifluoromethyl)phthalazin-1(2H)-onyl, pyrrolo[1,2-d][1,2,4]triazin-1(2H)-onyl, 1,2,3,4-tetrahydroisoquinolinyl, 2,3-dihydrobenzo[b][1,4]dioxinyl, 5,6,7,8-tetrahydrophthalazin-1(2H)-onyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, 5,6,7,8-tetrahydroimidazo[1,5-a]pyrazinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, indolizinyl, pyranopyrrolyl, 4H-quinolizinyl, purinyl, naphthyridinyl, pyridopyridinyl (including pyrido[3,4-b]-pyridinyl, pyrido[3,2-b]-pyridinyl, or pyrido[4,3-b]-pyridinyl), and pteridinyl. Other examples of fused-ring heterocyclyls include benzo-fused heterocyclyls, such as benzimidazolyl, benzo[d][1,3]dioxolyl, indolyl, isoindolyl (isobenzazolyl, pseudoisoindolyl), indoleninyl (pseudoindolyl), isoindazolyl (benzpyrazolyl), benzazinyl (including quinolinyl (1-benzazinyl) or isoquinolinyl (2-benzazinyl)), phthalazinyl, quinoxalinyl, quinazolinyl, benzodiazinyl (including cinnolinyl (1,2-benzodiazinyl) or quinazolinyl (1,3-benzodiazinyl)), benzopyranyl (including chromanyl or isochromanyl), benzoxazinyl (including 1,3,2-benzoxazinyl, 1,4,2-benzoxazinyl, 2,3,1-benzoxazinyl, or 3,1,4-benzoxazinyl), and benzisoxazinyl (including 1,2-benzisoxazinyl or 1,4-benzisoxazinyl). Examples of spirocyclic heterocyclyls include 1,4-dioxa-8-azaspiro[4.5]decanyl.

The term “5-6 membered heteroaryl” (alone or in combination with another term(s)) means aromatic heterocyclyl containing a total of 5 to 6 ring atoms. At least one of the ring atoms is a heteroatom (i.e., oxygen, nitrogen, or sulfur), with the remaining ring atoms being independently selected from the group consisting of carbon, oxygen, nitrogen, and sulfur.

The term “heterocycloalkyl” (alone or in combination with another term(s)) means a saturated heterocyclyl.

The term “heteroaryl” (alone or in combination with another term(s)) means an aromatic heterocyclyl containing from 5 to 14 ring atoms. A heteroaryl may be a single ring or 2 or 3 fused rings. Examples of heteroaryl substituents include 6-membered ring substituents such as pyridyl, pyrazyl, pyrimidinyl, pyridazinyl, and 1,3,5-, 1,2,4- or 1,2,3-triazinyl; 5-membered ring substituents such as imidazyl, furanyl, thiophenyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, 1,2,3-, 1,2,4-, 1,2,5-, or 1,3,4-oxadiazolyl and isothiazolyl; 6/5-membered fused ring substituents such as benzothiofuranyl, benzisoxazolyl, benzoxazolyl, and purinyl; and 6/6-membered fused rings such as benzopyranyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl, and benzoxazinyl.

A prefix attached to a multi-component substituent only applies to the first component. To illustrate, the term “alkylcycloalkyl” contains two components: alkyl and cycloalkyl. Thus, the C₁-C₆- prefix on C₁-C₆-alkylcycloalkyl means that the alkyl component of the alkylcycloalkyl contains from 1 to 6 carbon atoms; the C₁-C₆-prefix does not describe the cycloalkyl component. To illustrate further, the prefix “halo” on haloalkyloxyalkyl indicates that only the alkyloxy component of the alkyloxyalkyl substituent is substituted with one or more halogen radicals. If halogen substitution may alternatively or additionally occur on the alkyl component, the substituent would instead be described as “halogen-substituted alkyloxyalkyl” rather than “haloalkyloxyalkyl.” And finally, if the halogen substitution may only occur on the alkyl component, the substituent would instead be described as “alkyloxyhaloalkyl.”

The terms “treat”, “treating” and “treatment” refer to a method of alleviating or abrogating a disease and/or its attendant symptoms.

The terms “prevent”, “preventing” and “prevention” refer to a method of preventing the onset of a disease and/or its attendant symptoms or barring a subject from acquiring a disease. As used herein, “prevent”, “preventing” and “prevention” also include delaying the onset of a disease and/or its attendant symptoms and reducing a subject's risk of acquiring a disease.

The term “therapeutically effective amount” refers to that amount of the compound being administered sufficient to prevent development of or alleviate to some extent one or more of the symptoms of the condition or disorder being treated.

The term “modulate” refers to the ability of a compound to increase or decrease the function, or activity, of a kinase. “Modulation”, as used herein in its various forms, is intended to encompass antagonism, agonism, partial antagonism and/or partial agonism of the activity associated with kinase. Kinase inhibitors are compounds that, e.g., bind to, partially or totally block stimulation, decrease, prevent, delay activation, inactivate, desensitize, or down regulate signal transduction. Kinase activators are compounds that, e.g., bind to, stimulate, increase, open, activate, facilitate, enhance activation, sensitize or up regulate signal transduction.

The term “composition” as used herein is intended to encompass a product comprising the specified ingredients in the specified amounts, as well as any product which results, directly or indirectly, from combination of the specified ingredients in the specified amounts. By “pharmaceutically acceptable” it is meant the carrier, diluent or excipient must be compatible with the other ingredients of the formulation and not deleterious to the recipient thereof.

The “subject” is defined herein to include animals such as mammals, including, but not limited to, primates (e.g., humans), cows, sheep, goats, horses, dogs, cats, rabbits, rats, mice and the like. In preferred embodiments, the subject is a human.

Isotope Enriched or Labeled Compounds

Compounds of the invention can exist in isotope-labeled or -enriched form containing one or more atoms having an atomic mass or mass number different from the atomic mass or mass number most abundantly found in nature. Isotopes can be radioactive or non-radioactive isotopes. Isotopes of atoms such as hydrogen, carbon, phosphorous, sulfur, fluorine, chlorine, and iodine include, but are not limited to, ²H, ³H, ¹³C, ¹⁴C, ¹⁵N, ¹⁸O, ³²P, ³⁵S, ¹⁸F, ³⁶Cl and ¹²⁵I. Compounds that contain other isotopes of these and/or other atoms are within the scope of this invention.

In another embodiment, the isotope-labeled compounds contain deuterium (²H), tritium (³H) or ¹⁴C isotopes. Isotope-labeled compounds of this invention can be prepared by the general methods well known to persons having ordinary skill in the art. Such isotope-labeled compounds can be conveniently prepared by carrying out the procedures disclosed in the Examples disclosed herein and Schemes by substituting a readily available isotope-labeled reagent for a non-labeled reagent. In some instances, compounds may be treated with isotope-labeled reagents to exchange a normal atom with its isotope, for example, hydrogen for deuterium can be exchanged by the action of a deuteric acid such as D₂SO₄/D₂O. In addition to the above, relevant procedures and intermediates are disclosed, for instance, in Lizondo, J et al., Drugs Fut, 21(11), 1116 (1996); Brickner, S J et al., J Med Chem, 39(3), 673 (1996); Mallesham, B et al., Org Lett, 5(7), 963 (2003); PCT publications WO1997010223, WO2005099353, WO1995007271, WO2006008754; U.S. Pat. Nos. 7,538,189; 7,534,814; 7531685; 7528131; 7521421; 7514068; 7511013; and US Patent Application Publication Nos. 20090137457; 20090131485; 20090131363; 20090118238; 20090111840; 20090105338; 20090105307; 20090105147; 20090093422; 20090088416; and 20090082471, the methods are hereby incorporated by reference.

The isotope-labeled compounds of the invention may be used as standards to determine the effectiveness in binding assays. Isotope containing compounds have been used in pharmaceutical research to investigate the in vivo metabolic fate of the compounds by evaluation of the mechanism of action and metabolic pathway of the nonisotope-labeled parent compound (Blake et al. J. Pharm. Sci. 64, 3, 367-391 (1975)). Such metabolic studies are important in the design of safe, effective therapeutic drugs, either because the in vivo active compound administered to the patient or because the metabolites produced from the parent compound prove to be toxic or carcinogenic (Foster et al., Advances in Drug Research Vol. 14, pp. 2-36, Academic press, London, 1985; Kato et al., J. Labelled Comp. Radiopharmaceut., 36(10):927-932 (1995); Kushner et al., Can. J. Physiol. Pharmacol., 77, 79-88 (1999).

In addition, non-radio active isotope containing drugs, such as deuterated drugs called “heavy drugs,” can be used for the treatment of diseases and conditions related to NAMPT activity. Increasing the amount of an isotope present in a compound above its natural abundance is called enrichment. Examples of the amount of enrichment include from about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 21, 25, 29, 33, 37, 42, 46, 50, 54, 58, 63, 67, 71, 75, 79, 84, 88, 92, 96, to about 100 mol %. Replacement of up to about 15% of normal atom with a heavy isotope has been effected and maintained for a period of days to weeks in mammals, including rodents and dogs, with minimal observed adverse effects (Czajka D M and Finkel A J, Ann. N.Y. Acad. Sci. 1960 84: 770; Thomson J F, Ann. New York Acad. Sci 1960 84: 736; Czakja D M et al., Am. J. Physiol. 1961 201: 357). Acute replacement of as high as 15%-23% in human fluids with deuterium was found not to cause toxicity (Blagojevic N et al. in “Dosimetry & Treatment Planning for Neutron Capture Therapy”, Zamenhof R, Solares G and Harling 0 Eds. 1994. Advanced Medical Publishing, Madison Wis. pp. 125-134; Diabetes Metab. 23: 251 (1997)).

Stable isotope labeling of a drug can alter its physico-chemical properties such as pKa and lipid solubility. These effects and alterations can affect the pharmacodynamic response of the drug molecule if the isotopic substitution affects a region involved in a ligand-receptor interaction. While some of the physical properties of a stable isotope-labeled molecule are different from those of the unlabeled one, the chemical and biological properties are the same, with one important exception: because of the increased mass of the heavy isotope, any bond involving the heavy isotope and another atom will be stronger than the same bond between the light isotope and that atom. Accordingly, the incorporation of an isotope at a site of metabolism or enzymatic transformation will slow said reactions potentially altering the pharmacokinetic profile or efficacy relative to the non-isotopic compound.

Compounds

Suitable groups for X¹, X², Y¹, Z¹, R¹, and R² in compounds of all Formulas are independently selected. The described embodiments of the present invention may be combined. Such combination is contemplated and within the scope of the present invention. For example, it is contemplated that embodiments for any of X¹, X², Y¹, Z¹, R¹, and R² can be combined with embodiments defined for any other of X¹, X², Y¹, Z¹, R¹, and R².

Embodiments of Formula (I)

One embodiment of this invention, therefore, pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (I)

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is C(O)NH, or NHC(O);

Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl;

R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I;

R² is independently selected from the group consisting of C₄-C₆-alkyl, C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl, and 5-6 membered heteroaryl; wherein each R² C₄-C₆-alkyl, C₄-C₆-alkenyl, and C₄-C₆-alkynyl is substituted with one or more substituents independently selected from the group consisting of R³, OR³, SR³, S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂, NHR³, N(R³)₂, NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³, NR³C(O)OR³, NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³, NR³C(O)N(R³)₂, C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³, C(O)NHSO₂R³, C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I;

R³, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and heterocyclyl; wherein each R³ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁵, OR⁵, SR⁵, S(O)R⁵, SO₂R⁵, C(O)R⁵, CO(O)R⁵, OC(O)R⁵, OC(O)OR⁵, NH₂, NHR⁵, N(R⁵)₂, NHC(O)R⁵, NR⁵C(O)R⁵, NHS(O)₂R⁵, NR⁵S(O)₂R⁵, NHC(O)OR⁵, NR⁵C(O)OR⁵, NHC(O)NH₂, NHC(O)NHR⁵, NHC(O)N(R⁵)₂, NR⁵C(O)NHR⁵, NR⁵C(O)N(R⁵)₂, C(O)NH₂, C(O)NHR⁵, C(O)N(R⁵)₂, C(O)NHOH, C(O)NHOR⁵, C(O)NHSO₂R⁵, C(O)NR⁵SO₂R⁵, SO₂NH₂, SO₂NHR⁵, SO₂N(R⁵)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁵, C(N)N(R⁵)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R³ aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁶, OR⁶, SR⁶, S(O)R⁶, SO₂R⁶, C(O)R⁶, CO(O)R⁶, OC(O)R⁶, OC(O)OR⁶, NH₂, NHR⁶, N(R⁶)₂, NHC(O)R⁶, NR⁶C(O)R⁶, NHS(O)₂R⁶, NR⁶S(O)₂R⁶, NHC(O)OR⁶, NR⁶C(O)OR⁶, NHC(O)NH₂, NHC(O)NHR⁶, NHC(O)N(R⁶)₂, NR⁶C(O)NHR⁶, NR⁶C(O)N(R⁶)₂, C(O)NH₂, C(O)NHR⁶, C(O)N(R⁶)₂, C(O)NHOH, C(O)NHOR⁶, C(O)NHSO₂R⁶, C(O)NR⁶SO₂R⁶, SO₂NH₂, SO₂NHR⁶, SO₂N(R⁶)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁶, C(N)N(R⁶)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I;

R⁵, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁵ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁸, OR⁸, SR⁸, S(O)R⁸, SO₂R⁸, NHR⁸, N(R⁸)₂, C(O)R⁸, C(O)NH₂, C(O)NHR⁸, C(O)N(R⁸)₂, NHC(O)R⁸, NR⁸C(O)R⁸, NHSO₂R⁸, NHC(O)OR⁸, SO₂NH₂, SO₂NHR⁸, SO₂N(R⁸)₂, NHC(O)NH₂, NHC(O)NHR⁸, OH, (O), C(O)OH, N₃, CN, NH₂, F, Cl, Br and I;

R⁶, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁶ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁹, OR⁹, SR⁹, S(O)R⁹, SO₂R⁹, NHR⁹, N(R⁹)₂, C(O)R⁹, C(O)NH₂, C(O)NHR⁹, C(O)N(R⁹)₂, NHC(O)R⁹, NR⁹C(O)R⁹, NHSO₂R⁹, NHC(O)OR⁹, SO₂NH₂, SO₂NHR⁹, SO₂N(R⁹)₂, NHC(O)NH₂, NHC(O)NHR⁹, OH, (O), C(O)OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br and I;

R⁷, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

R⁸, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

R⁹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

wherein the cyclic moieties represented by R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹ are independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, C(O)C(O)R¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂ NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, CF₃, OCF₃, F, Cl, Br and I;

R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, OR¹³, C(O)OR¹³, OCF₃, CF₃, F, Cl, Br and I;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; and

R¹³, at each occurrence, is independently selected from the group consisting of alkyl, alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

with the proviso that when X¹ is CR¹ and X² is CR¹; R¹ is hydrogen; Y¹ is NHC(O); Z¹ is

and R² is pyrrolyl; the R² pyrrolyl is not substituted with two alkyl groups.

In one embodiment of Formula (I), X¹ is N and X² is CR¹; or X¹ is CR¹ and X² is N; or X¹ is CR¹ and X² is CR¹. In another embodiment of Formula (I), X¹ is N and X² is CR¹. In another embodiment of Formula (I), X¹ is CR¹ and X² is N. In another embodiment of Formula (I), X¹ is CR¹ and X² is CR¹.

In one embodiment of Formula (I), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I. In another embodiment of Formula (I), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, Cl, Br and I. In another embodiment of Formula (I), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, and F. In another embodiment of Formula (I), R¹, at each occurrence, is hydrogen.

In one embodiment of Formula (I), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I. In another embodiment of Formula (I), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, Cl, Br and I. In another embodiment of Formula (I), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, and F. In another embodiment of Formula (I), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is hydrogen.

In one embodiment of Formula (I), Y¹ is C(O)NH, or NHC(O). In another embodiment of Formula (I), Y¹ is C(O)NH. In another embodiment of Formula (I), Y¹ is NHC(O).

In one embodiment of Formula (I), Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl. In another embodiment of Formula (I), Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl. In another embodiment of Formula (I), Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl. In another embodiment of Formula (I), Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl.

In one embodiment of Formula (I), R² is independently selected from the group consisting of C₄-C₆-alkyl, C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl, and 5-6 membered heteroaryl; wherein each R² C₄-C₆-alkyl, C₄-C₆-alkenyl, and C₄-C₆-alkynyl is substituted with one or more substituents independently selected from the group consisting of R³, OR³, SR³, S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂, NHR³, N(R³)₂, NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³, NR³C(O)OR³, NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³, NR³C(O)N(R³)₂, C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³, C(O)NHSO₂R³, C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I. In another embodiment of Formula (I), R² is aryl; wherein each R² aryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, F, Cl, and I. In another embodiment of Formula (I), R² is aryl; wherein each R² aryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, and SO₂R⁴. In another embodiment of Formula (I), R² is phenyl; wherein each R² phenyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, and SO₂R⁴.

In another embodiment of Formula (I), R² is 5-6 membered heteroaryl; wherein each R² 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, F, Cl, and I. In another embodiment of Formula (I), R² is 5-6 membered heteroaryl; wherein each R² 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, and SO₂R⁴. In another embodiment of Formula (I), R² is furanyl or thiophenyl; wherein each R² furanyl and thiophenyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, and SO₂R⁴.

In one embodiment of Formula (I), R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I. In another embodiment of Formula (I), R⁴, at each occurrence, is heterocyclyl.

In one embodiment of Formula (I), each R⁴ heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with alkyl or alkoxy; and R¹², at each occurrence, is independently selected alkyl. In another embodiment of Formula (I), each R⁴ heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, (C(O)C(O)R¹⁰, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl, are optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, SO₂R¹¹, NH₂, N(R¹¹)₂, NHC(O)R¹¹, NHS(O)₂R¹¹, OH, NO₂, and F; wherein each R¹⁰ aryl, heterocyclyl and cycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², C(O)R¹², OH, CN, CF₃, OCF₃, F, and Cl; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹¹ alkyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, C(O)OR¹³, OCF₃, CF₃, F, and Cl; R¹², at each occurrence, is independently selected from the group consisting of alkyl and aryl; and R¹³, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl.

One embodiment of this invention pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (I)

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is C(O)NH, or NHC(O);

Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl;

R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, and F;

R² is aryl or 5-6 membered heteroaryl wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, SO₂R⁴, and OR⁴;

R⁴, at each occurrence, is heterocyclyl;

wherein the cyclic moiety represented by R⁴ is independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, C(O)R¹⁰, C(O)C(O)R¹⁰, and CO(O)R¹⁰;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, SO₂R¹¹, NH₂, N(R¹¹)₂, NHC(O)R¹¹, NHS(O)₂R¹¹, OH, NO₂, and F; wherein each R¹⁰ aryl, heterocyclyl and cycloalkyl is optionally substituted with one or more R¹², OR¹², C(O)R¹², OH, CN, CF₃, OCF₃, F, and Cl;

R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹¹ alkyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, C(O)OR¹³, OCF₃, CF₃, F, and Cl;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, and aryl; and

R¹³, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl.

Still another embodiment pertains to compounds having Formula (I), which includes Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, and pharmaceutically acceptable salts thereof.

Embodiments of Formula (II)

In another aspect, the present invention provides compounds of Formula (II)

and pharmaceutically acceptable salts thereof; wherein X¹, X², Y¹, R¹, and R² are as described herein for Formula (I).

One embodiment of this invention pertains to compounds of Formula (II) and pharmaceutically acceptable salts thereof;

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is C(O)NH, or NHC(O);

R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I;

R² is independently selected from the group consisting of C₄-C₆-alkyl, C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl, and 5-6 membered heteroaryl; wherein each R² C₄-C₆-alkyl, C₄-C₆-alkenyl, and C₄-C₆-alkynyl is substituted with one or more substituents independently selected from the group consisting of R³, OR³, SR³, S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂, NHR³, N(R³)₂, NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³, NR³C(O)OR³, NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³, NR³C(O)N(R³)₂, C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³, C(O)NHSO₂R³, C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I;

R³, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and heterocyclyl; wherein each R³ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁵, OR⁵, SR⁵, S(O)R⁵, SO₂R⁵, C(O)R⁵, CO(O)R⁵, OC(O)R⁵, OC(O)OR⁵, NH₂, NHR⁵, N(R⁵)₂, NHC(O)R⁵, NR⁵C(O)R⁵, NHS(O)₂R⁵, NR⁵S(O)₂R⁵, NHC(O)OR⁵, NR⁵C(O)OR⁵, NHC(O)NH₂, NHC(O)NHR⁵, NHC(O)N(R⁵)₂, NR⁵C(O)NHR⁵, NR⁵C(O)N(R⁵)₂, C(O)NH₂, C(O)NHR⁵, C(O)N(R⁵)₂, C(O)NHOH, C(O)NHOR⁵, C(O)NHSO₂R⁵, C(O)NR⁵SO₂R⁵, SO₂NH₂, SO₂NHR⁵, SO₂N(R⁵)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁵, C(N)N(R⁵)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R³ aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁶, OR⁶, SR⁶, S(O)R⁶, SO₂R⁶, C(O)R⁶, CO(O)R⁶, OC(O)R⁶, OC(O)OR⁶, NH₂, NHR⁶, N(R⁶)₂, NHC(O)R⁶, NR⁶C(O)R⁶, NHS(O)₂R⁶, NR⁶S(O)₂R⁶, NHC(O)OR⁶, NR⁶C(O)OR⁶, NHC(O)NH₂, NHC(O)NHR⁶, NHC(O)N(R⁶)₂, NR⁶C(O)NHR⁶, NR⁶C(O)N(R⁶)₂, C(O)NH₂, C(O)NHR⁶, C(O)N(R⁶)₂, C(O)NHOH, C(O)NHOR⁶, C(O)NHSO₂R⁶, C(O)NR⁶SO₂R⁶, SO₂NH₂, SO₂NHR⁶, SO₂N(R⁶)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁶, C(N)N(R⁶)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I;

R⁵, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁵ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁸, OR⁸, SR⁸, S(O)R⁸, SO₂R⁸, NHR⁸, N(R⁸)₂, C(O)R⁸, C(O)NH₂, C(O)NHR⁸, C(O)N(R⁸)₂, NHC(O)R⁸, NR⁸C(O)R⁸, NHSO₂R⁸, NHC(O)OR⁸, SO₂NH₂, SO₂NHR⁸, SO₂N(R⁸)₂, NHC(O)NH₂, NHC(O)NHR⁸, OH, (O), C(O)OH, N₃, CN, NH₂, F, Cl, Br and I;

R⁶, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁶ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁹, OR⁹, SR⁹, S(O)R⁹, SO₂R⁹, NHR⁹, N(R⁹)₂, C(O)R⁹, C(O)NH₂, C(O)NHR⁹, C(O)N(R⁹)₂, NHC(O)R⁹, NR⁹C(O)R⁹, NHSO₂R⁹, NHC(O)OR⁹, SO₂NH₂, SO₂NHR⁹, SO₂N(R⁹)₂, NHC(O)NH₂, NHC(O)NHR⁹, OH, (O), C(O)OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br and I;

R⁷, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

R⁸, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

R⁹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

wherein the cyclic moieties represented by R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹ are independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, C(O)C(O)R¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂ NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, CF₃, OCF₃, F, Cl, Br and I;

R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, OR¹³, C(O)OR¹³, OCF₃, CF₃, F, Cl, Br and I;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; and R¹³, at each occurrence, is independently selected from the group consisting of alkyl, alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl.

In one embodiment of Formula (II), X¹ is N and X² is CR¹; or X¹ is CR¹ and X² is N; or X¹ is CR¹ and X² is CR¹. In another embodiment of Formula (II), X¹ is N and X² is CR¹. In another embodiment of Formula (II), X¹ is CR¹ and X² is N. In another embodiment of Formula (II), X¹ is CR¹ and X² is CR¹.

In one embodiment of Formula (II), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I. In another embodiment of Formula (II), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, Cl, Br and I. In another embodiment of Formula (II), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, and F. In another embodiment of Formula (II), R¹, at each occurrence, is hydrogen.

In one embodiment of Formula (II), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I. In another embodiment of Formula (II), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, Cl, Br and I. In another embodiment of Formula (II), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, and F. In another embodiment of Formula (II), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is hydrogen.

In one embodiment of Formula (II), Y¹ is C(O)NH, or NHC(O). In another embodiment of Formula (II), Y¹ is C(O)NH. In another embodiment of Formula (II), Y¹ is NHC(O).

In one embodiment of Formula (II), R² is independently selected from the group consisting of C₄-C₆-alkyl, C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl, and 5-6 membered heteroaryl; wherein each R² C₄-C₆-alkyl, C₄-C₆-alkenyl, and C₄-C₆-alkynyl is substituted with one or more substituents independently selected from the group consisting of R³, OR³, SR³, S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂, NHR³, N(R³)₂, NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³, NR³C(O)OR³, NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³, NR³C(O)N(R³)₂, C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³, C(O)NHSO₂R³, C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I. In another embodiment of Formula (II), R² is aryl; wherein each R² aryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, F, Cl, and I. In another embodiment of Formula (II), R² is aryl; wherein each R² aryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, and SO₂R⁴. In another embodiment of Formula (II), R² is phenyl; wherein each R² phenyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, and SO₂R⁴.

In another embodiment of Formula (II), R² is 5-6 membered heteroaryl; wherein each R² 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, F, Cl, and I. In another embodiment of Formula (II), R² is 5-6 membered heteroaryl; wherein each R² 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, and SO₂R⁴. In another embodiment of Formula (II), R² is furanyl or thiophenyl; wherein each R² furanyl and thiophenyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, and SO₂R⁴.

In one embodiment of Formula (II), R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I. In another embodiment of Formula (II), R⁴, at each occurrence, is heterocyclyl.

In one embodiment of Formula (II), each R⁴ heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂ NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with alkyl or alkoxy; and R¹², at each occurrence, is independently selected alkyl. In another embodiment of Formula (II), each R⁴ heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, C(O)C(O)R¹⁰, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl, are optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, SO₂R¹¹, NH₂, N(R¹¹)₂, NHC(O)R¹¹, NHS(O)₂R¹¹, OH, NO₂, and F; wherein each R¹⁰ aryl, heterocyclyl and cycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², C(O)R¹², OH, CN, CF₃, OCF₃, F, and Cl; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹¹ alkyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, C(O)OR¹³, OCF₃, CF₃, F, and Cl; R¹², at each occurrence, is independently selected from the group consisting of alkyl and aryl; and R¹³, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl.

One embodiment of this invention pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (II)

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is C(O)NH, or NHC(O);

R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, and F;

R² is aryl or 5-6 membered heteroaryl wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, SO₂R⁴, and OR⁴;

R⁴, at each occurrence, is heterocyclyl;

wherein the cyclic moiety represented by R⁴ is independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, C(O)R¹⁰, C(O)C(O)R¹⁰, and CO(O)R¹⁰;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, SO₂R¹¹, NH₂, N(R¹¹)₂, NHC(O)R¹¹, NHS(O)₂R¹¹, OH, NO₂, and F; wherein each R¹⁰ aryl, heterocyclyl and cycloalkyl is optionally substituted with one or more R¹², OR¹², C(O)R¹², OH, CN, CF₃, OCF₃, F, and Cl; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹¹ alkyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, C(O)OR¹³, OCF₃, CF₃, F, and Cl;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, and aryl; and

R¹³, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl.

Still another embodiment pertains to compounds having Formula (II), which includes Examples 1, 2, 3, 4, 5, 6, 7, 10, 20, 21, 22, 23, 24, 25, 26, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 609, 610, 611, 612, 613, and pharmaceutically acceptable salts thereof.

Embodiments of Formula (III)

In another aspect, the present invention provides compounds of Formula (III)

and pharmaceutically acceptable salts thereof; wherein Y¹ is as described in Formula (I) herein and R^(4x) is as described herein for substituents on R² when R² is aryl in Formula (I).

One embodiment of this invention pertains to compounds of Formula (III) or pharmaceutically acceptable salts thereof;

wherein

Y¹ is C(O)NH, or NHC(O);

R^(4x) is independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I;

R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I;

R⁷, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

wherein the cyclic moieties represented by R⁴ and R⁷ are independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, C(O)C(O)R¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, CF₃, OCF₃, F, Cl, Br and I;

R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, OR¹³, C(O)OR¹³, OCF₃, CF₃, F, Cl, Br and I;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; and

R¹³, at each occurrence, is independently selected from the group consisting of alkyl, alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl.

In one embodiment of Formula (III), Y¹ is C(O)NH, or NHC(O). In another embodiment of Formula (III), Y¹ is C(O)NH. In another embodiment of Formula (III), Y¹ is NHC(O).

In one embodiment of Formula (III), R^(4x) is selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I. In another embodiment of Formula (III), R^(4x) is selected from the group consisting of R⁴, OR⁴, SO₂R⁴, F, Cl, and I. In another embodiment of Formula (III), R^(4x) is selected from the group consisting of R⁴, SO₂R⁴, and OR⁴.

In one embodiment of Formula (III), R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I. In another embodiment of Formula (III), R⁴, at each occurrence, is heterocyclyl.

In one embodiment of Formula (III), each R⁴ heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂ NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with alkyl or alkoxy; and R¹², at each occurrence, is independently selected alkyl. In another embodiment of Formula (III), each R⁴ heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, C(O)C(O)R¹⁰, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl, are optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, SO₂R¹¹, NH₂, N(R¹¹)₂, NHC(O)R¹¹, NHS(O)₂R¹¹, OH, NO₂, and F; wherein each R¹⁰ aryl, heterocyclyl and cycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², C(O)R¹², OH, CN, CF₃, OCF₃, F, and Cl; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹¹ alkyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, C(O)OR¹³, OCF₃, CF₃, F, and Cl; R¹², at each occurrence, is independently selected from the group consisting of alkyl and aryl; and R¹³, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl.

One embodiment of this invention pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (III)

wherein

Y¹ is C(O)NH, or NHC(O);

R^(4x) is independently selected from the group consisting of R⁴, SO₂R⁴, and OR⁴;

R⁴, at each occurrence, is heterocyclyl;

wherein the cyclic moiety represented by R⁴ is independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, C(O)R¹⁰, C(O)C(O)R¹⁰, and CO(O)R¹⁰;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, SO₂R¹¹, NH₂, N(R¹¹)₂, NHC(O)R¹¹, NHS(O)₂R¹¹, OH, NO₂, and F; wherein each R¹⁰ aryl, heterocyclyl and cycloalkyl is optionally substituted with one or more R¹², OR¹², C(O)R¹², OH, CN, CF₃, OCF₃, F, and Cl;

R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹¹ alkyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, C(O)OR¹³, OCF₃, CF₃, F, and Cl;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, and aryl; and

R¹³, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl.

Still another embodiment pertains to compounds having Formula (III), which includes Examples 1, 2, 3, 4, 5, 6, 7, 10, 20, 21, 22, 23, 24, 25, 26, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 602, 609, 610, and pharmaceutically acceptable salts thereof.

Embodiments of Formula (IV)

In another aspect, the present invention provides compounds of Formula (IV)

and pharmaceutically acceptable salts thereof; wherein X¹, X², Y¹, R¹, and R² are as described herein for Formula (I).

One embodiment of this invention pertains to compounds of Formula (IV) and pharmaceutically acceptable salts thereof;

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is C(O)NH, or NHC(O);

R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I;

R² is independently selected from the group consisting of C₄-C₆-alkyl, C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl, and 5-6 membered heteroaryl; wherein each R² C₄-C₆-alkyl, C₄-C₆-alkenyl, and C₄-C₆-alkynyl is substituted with one or more substituents independently selected from the group consisting of R³, OR³, SR³, S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂, NHR³, N(R³)₂, NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³, NR³C(O)OR³, NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³, NR³C(O)N(R³)₂, C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³, C(O)NHSO₂R³, C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I;

R³, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and heterocyclyl; wherein each R³ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁵, OR⁵, SR⁵, S(O)R⁵, SO₂R⁵, C(O)R⁵, CO(O)R⁵, OC(O)R⁵, OC(O)OR⁵, NH₂, NHR⁵, N(R⁵)₂, NHC(O)R⁵, NR⁵C(O)R⁵, NHS(O)₂R⁵, NR⁵S(O)₂R⁵, NHC(O)OR⁵, NR⁵C(O)OR⁵, NHC(O)NH₂, NHC(O)NHR⁵, NHC(O)N(R⁵)₂, NR⁵C(O)NHR⁵, NR⁵C(O)N(R⁵)₂, C(O)NH₂, C(O)NHR⁵, C(O)N(R⁵)₂, C(O)NHOH, C(O)NHOR⁵, C(O)NHSO₂R⁵, C(O)NR⁵SO₂R⁵, SO₂NH₂, SO₂NHR⁵, SO₂N(R⁵)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁵, C(N)N(R⁵)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R³ aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁶, OR⁶, SR⁶, S(O)R⁶, SO₂R⁶, C(O)R⁶, CO(O)R⁶, OC(O)R⁶, OC(O)OR⁶, NH₂, NHR⁶, N(R⁶)₂, NHC(O)R⁶, NR⁶C(O)R⁶, NHS(O)₂R⁶, NR⁶S(O)₂R⁶, NHC(O)OR⁶, NR⁶C(O)OR⁶, NHC(O)NH₂, NHC(O)NHR⁶, NHC(O)N(R⁶)₂, NR⁶C(O)NHR⁶, NR⁶C(O)N(R⁶)₂, C(O)NH₂, C(O)NHR⁶, C(O)N(R⁶)₂, C(O)NHOH, C(O)NHOR⁶, C(O)NHSO₂R⁶, C(O)NR⁶SO₂R⁶, SO₂NH₂, SO₂NHR⁶, SO₂N(R⁶)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁶, C(N)N(R⁶)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I;

R⁵, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁵ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁸, OR⁸, SR⁸, S(O)R⁸, SO₂R⁸, NHR⁸, N(R⁸)₂, C(O)R⁸, C(O)NH₂, C(O)NHR⁸, C(O)N(R⁸)₂, NHC(O)R⁸, NR⁸C(O)R⁸, NHSO₂R⁸, NHC(O)OR⁸, SO₂NH₂, SO₂NHR⁸, SO₂N(R⁸)₂, NHC(O)NH₂, NHC(O)NHR⁸, OH, (O), C(O)OH, N₃, CN, NH₂, F, Cl, Br and I;

R⁶, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁶ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁹, OR⁹, SR⁹, S(O)R⁹, SO₂R⁹, NHR⁹, N(R⁹)₂, C(O)R⁹, C(O)NH₂, C(O)NHR⁹, C(O)N(R⁹)₂, NHC(O)R⁹, NR⁹C(O)R⁹, NHSO₂R⁹, NHC(O)OR⁹, SO₂NH₂, SO₂NHR⁹, SO₂N(R⁹)₂, NHC(O)NH₂, NHC(O)NHR⁹, OH, (O), C(O)OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br and I;

R⁷, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

R⁸, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; R⁹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

wherein the cyclic moieties represented by R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹ are independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, C(O)C(O)R¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, CF₃, OCF₃, F, Cl, Br and I;

R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, OR¹³, C(O)OR¹³, OCF₃, CF₃, F, Cl, Br and I;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; and

R¹³, at each occurrence, is independently selected from the group consisting of alkyl, alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl.

In one embodiment of Formula (IV), X¹ is N and X² is CR¹; or X¹ is CR¹ and X² is N; or X¹ is CR¹ and X² is CR¹. In another embodiment of Formula (IV), X¹ is N and X² is CR¹. In another embodiment of Formula (IV), X¹ is CR¹ and X² is N. In another embodiment of Formula (IV), X¹ is CR¹ and X² is CR¹.

In one embodiment of Formula (IV), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I. In another embodiment of Formula (IV), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, Cl, Br and I. In another embodiment of Formula (IV), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, and F. In another embodiment of Formula (IV), R¹, at each occurrence, is hydrogen.

In one embodiment of Formula (IV), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I. In another embodiment of Formula (IV), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, Cl, Br and I. In another embodiment of Formula (IV), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, and F. In another embodiment of Formula (IV), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is hydrogen.

In one embodiment of Formula (IV), Y¹ is C(O)NH, or NHC(O). In another embodiment of Formula (IV), Y¹ is C(O)NH. In another embodiment of Formula (IV), Y¹ is NHC(O).

In one embodiment of Formula (IV), R² is independently selected from the group consisting of C₄-C₆-alkyl, C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl, and 5-6 membered heteroaryl; wherein each R² C₄-C₆-alkyl, C₄-C₆-alkenyl, and C₄-C₆-alkynyl is substituted with one or more substituents independently selected from the group consisting of R³, OR³, SR³, S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂, NHR³, N(R³)₂, NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³, NR³C(O)OR³, NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³, NR³C(O)N(R³)₂, C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³, C(O)NHSO₂R³, C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I. In another embodiment of Formula (IV), R² is aryl; wherein each R² aryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, F, Cl, and I. In another embodiment of Formula (IV), R² is aryl; wherein each R² aryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, and SO₂R⁴. In another embodiment of Formula (IV), R² is phenyl; wherein each R² phenyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, and SO₂R⁴.

In another embodiment of Formula (IV), R² is 5-6 membered heteroaryl; wherein each R² 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, F, Cl, and I. In another embodiment of Formula (IV), R² is 5-6 membered heteroaryl; wherein each R² 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, and SO₂R⁴. In another embodiment of Formula (IV), R² is furanyl or thiophenyl; wherein each R² furanyl and thiophenyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, and SO₂R⁴.

In one embodiment of Formula (IV), R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I. In another embodiment of Formula (IV), R⁴, at each occurrence, is heterocyclyl.

In one embodiment of Formula (IV), each R⁴ heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂ NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with alkyl or alkoxy; and R¹², at each occurrence, is independently selected alkyl. In another embodiment of Formula (IV), each R⁴ heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, C(O)C(O)R¹⁰, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl, are optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, SO₂R¹¹, NH₂, N(R¹¹)₂, NHC(O)R¹¹, NHS(O)₂R¹¹, OH, NO₂, and F; wherein each R¹⁰ aryl, heterocyclyl and cycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², C(O)R¹², OH, CN, CF₃, OCF₃, F, and Cl; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹¹ alkyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, C(O)OR¹³, OCF₃, CF₃, F, and Cl; R¹², at each occurrence, is independently selected from the group consisting of alkyl and aryl; and R¹³, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl.

One embodiment of this invention pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (IV)

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is C(O)NH, or NHC(O);

R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, and F;

R² is aryl or 5-6 membered heteroaryl wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, SO₂R⁴, and OR⁴;

R⁴, at each occurrence, is heterocyclyl;

wherein the cyclic moiety represented by R⁴ is independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, C(O)R¹⁰, C(O)C(O)R¹⁰, and CO(O)R¹⁰;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, SO₂R¹¹, NH₂, N(R¹¹)₂, NHC(O)R¹¹, NHS(O)₂R¹¹, OH, NO₂, and F; wherein each R¹⁰ aryl, heterocyclyl and cycloalkyl is optionally substituted with one or more R¹², OR¹², C(O)R¹², OH, CN, CF₃, OCF₃, F, and Cl;

R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹¹ alkyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, C(O)OR¹³, OCF₃, CF₃, F, and Cl;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, and aryl; and

R¹³, at each occurrence, is independently selected from the group consisting of alkyl, and heterocyclyl;

with the proviso that when X¹ is CR¹ and X² is CR¹; R¹ is hydrogen; Y¹ is NHC(O); and R² is pyrrolyl; the R² pyrrolyl is not substituted with two alkyl groups.

Still another embodiment pertains to compounds having Formula (IV), which includes Examples 8, 9, 11, 12, 13, 14, 15, 16, 17, 18, 19, 27, 28, 141, 142, 204, 310, 311, 312, 313, and pharmaceutically acceptable salts thereof.

Embodiments of Formula (IA)

One embodiment of this invention, therefore, pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (IA)

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is C(O)NH, or NHC(O);

Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl;

R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I;

R² is independently selected from the group consisting of C₄-C₆-alkyl, C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl, and 5-6 membered heteroaryl; wherein each R² C₄-C₆-alkyl, C₄-C₆-alkenyl, and C₄-C₆-alkynyl is substituted with one or more substituents independently selected from the group consisting of R³, OR³, SR³, S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂, NHR³, N(R³)₂, NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³, NR³C(O)OR³, NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³, NR³C(O)N(R³)₂, C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³, C(O)NHSO₂R³, C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I;

R³, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and heterocyclyl; wherein each R³ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁵, OR⁵, SR⁵, S(O)R⁵, SO₂R⁵, C(O)R⁵, CO(O)R⁵, OC(O)R⁵, OC(O)OR⁵, NH₂, NHR⁵, N(R⁵)₂, NHC(O)R⁵, NR⁵C(O)R⁵, NHS(O)₂R⁵, NR⁵S(O)₂R⁵, NHC(O)OR⁵, NR⁵C(O)OR⁵, NHC(O)NH₂, NHC(O)NHR⁵, NHC(O)N(R⁵)₂, NR⁵C(O)NHR⁵, NR⁵C(O)N(R⁵)₂, C(O)NH₂, C(O)NHR⁵, C(O)N(R⁵)₂, C(O)NHOH, C(O)NHOR⁵, C(O)NHSO₂R⁵, C(O)NR⁵SO₂R⁵, SO₂NH₂, SO₂NHR⁵, SO₂N(R⁵)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁵, C(N)N(R⁵)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R³ aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁶, OR⁶, SR⁶, S(O)R⁶, SO₂R⁶, C(O)R⁶, CO(O)R⁶, OC(O)R⁶, OC(O)OR⁶, NH₂, NHR⁶, N(R⁶)₂, NHC(O)R⁶, NR⁶C(O)R⁶, NHS(O)₂R⁶, NR⁶S(O)₂R⁶, NHC(O)OR⁶, NR⁶C(O)OR⁶, NHC(O)NH₂, NHC(O)NHR⁶, NHC(O)N(R⁶)₂, NR⁶C(O)NHR⁶, NR⁶C(O)N(R⁶)₂, C(O)NH₂, C(O)NHR⁶, C(O)N(R⁶)₂, C(O)NHOH, C(O)NHOR⁶, C(O)NHSO₂R⁶, C(O)NR⁶SO₂R⁶, SO₂NH₂, SO₂NHR⁶, SO₂N(R⁶)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁶, C(N)N(R⁶)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I;

R⁵, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁵ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁸, OR⁸, SR⁸, S(O)R⁸, SO₂R⁸, NHR⁸, N(R⁸)₂, C(O)R⁸, C(O)NH₂, C(O)NHR⁸, C(O)N(R⁸)₂, NHC(O)R⁸, NR⁸C(O)R⁸, NHSO₂R⁸, NHC(O)OR⁸, SO₂NH₂, SO₂NHR⁸, SO₂N(R⁸)₂, NHC(O)NH₂, NHC(O)NHR⁸, OH, (O), C(O)OH, N₃, CN, NH₂, F, Cl, Br and I;

R⁶, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁶ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁹, OR⁹, SR⁹, S(O)R⁹, SO₂R⁹, NHR⁹, N(R⁹)₂, C(O)R⁹, C(O)NH₂, C(O)NHR⁹, C(O)N(R⁹)₂, NHC(O)R⁹, NR⁹C(O)R⁹, NHSO₂R⁹, NHC(O)OR⁹, SO₂NH₂, SO₂NHR⁹, SO₂N(R⁹)₂, NHC(O)NH₂, NHC(O)NHR⁹, OH, (O), C(O)OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br and I;

R⁷, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

R⁸, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

R⁹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

wherein the cyclic moieties represented by R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹ are independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, C(O)C(O)R¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, CF₃, OCF₃, F, Cl, Br and I;

R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, OR¹³, C(O)OR¹³, OCF₃, CF₃, F, Cl, Br and I;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; and

R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; with the proviso that when X¹ is CR¹ and X² is CR¹; R¹ is hydrogen; Y¹ is NHC(O); Z¹ is

and R² is pyrrolyl; the R² pyrrolyl is not substituted with two alkyl groups.

In one embodiment of Formula (IA), X¹ is N and X² is CR¹; or X¹ is CR¹ and X² is N; or X¹ is CR¹ and X² is CR¹. In another embodiment of Formula (IA), X¹ is N and X² is CR¹. In another embodiment of Formula (IA), X¹ is CR¹ and X² is N. In another embodiment of Formula (IA), X¹ is CR¹ and X² is CR¹.

In one embodiment of Formula (IA), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I. In another embodiment of Formula (IA), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, Cl, Br and I. In another embodiment of Formula (IA), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, and Cl. In another embodiment of Formula (IA), R¹, at each occurrence, is hydrogen.

In one embodiment of Formula (IA), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I. In another embodiment of Formula (IA), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, Cl, Br and I. In another embodiment of Formula (IA), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, and Cl. In another embodiment of Formula (IA), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is hydrogen.

In one embodiment of Formula (IA), Y¹ is C(O)NH, or NHC(O). In another embodiment of Formula (IA), Y¹ is C(O)NH. In another embodiment of Formula (IA), Y¹ is NHC(O).

In one embodiment of Formula (IA), Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl. In another embodiment of Formula (IA), Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl. In another embodiment of Formula (IA), Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl. In another embodiment of Formula (IA), Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl. In another embodiment of Formula (IA), Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl.

In one embodiment of Formula (IA), R² is independently selected from the group consisting of C₄-C₆-alkyl, C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl, and 5-6 membered heteroaryl; wherein each R² C₄-C₆-alkyl, C₄-C₆-alkenyl, and C₄-C₆-alkynyl is substituted with one or more substituents independently selected from the group consisting of R³, OR³, SR³, S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂, NHR³, N(R³)₂, NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³, NR³C(O)OR³, NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³, NR³C(O)N(R³)₂, C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³, C(O)NHSO₂R³, C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I. In another embodiment of Formula (IA), R² is aryl; wherein each R² aryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, F, Cl, and I. In another embodiment of Formula (IA), R² is aryl; wherein each R² aryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, and F. In another embodiment of Formula (IA), R² is phenyl; wherein each R² phenyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, and F. In another embodiment of Formula (IA), R² is phenyl; wherein each R² phenyl is substituted with one substituent independently selected from the group consisting of R⁴, OR⁴, and SO₂R⁴.

In another embodiment of Formula (IA), R² is 5-6 membered heteroaryl; wherein each R² 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, F, Cl, and I. In another embodiment of Formula (IA), R² is 5-6 membered heteroaryl; wherein each R² 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, and F. In another embodiment of Formula (IA), R² is furanyl or thiophenyl; wherein each R² furanyl and thiophenyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, and F.

In one embodiment of Formula (IA), R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I. In another embodiment of Formula (IA), R⁴, at each occurrence, is alkyl or heterocyclyl.

In one embodiment of Formula (IA), each R⁴ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I. In another embodiment of Formula (IA), each R⁴ alkyl is optionally substituted with one R⁷.

In one embodiment of Formula (IA), R⁷, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl. In another embodiment of Formula (IA), R⁷, at each occurrence, is heterocyclyl.

In one embodiment of Formula (IA), each R⁴ and R⁷ heterocyclyl is independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂ NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(C(O)N(R¹²)₂), C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, OR¹³, C(O)OR¹³, OCF₃, CF₃, F, Cl, Br and I; R¹², at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; and R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl.

In another embodiment of Formula (IA), each R⁴ and R⁷ heterocyclyl is independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, C(O)C(O)R¹⁰, OH, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl, are optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, SO_(Z)R¹¹, NH₂, N(R¹¹)₂, NHC(O)R¹¹, NHS(O)₂R¹¹, OH, NO₂, and F; wherein each R¹⁰ aryl, heterocyclyl and cycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², C(O)R¹², OH, CN, CF₃, OCF₃, F, and Cl; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹¹ alkyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, CF₃, F, and Cl; R¹², at each occurrence, is independently selected from the group consisting of alkyl and aryl; and R¹³, at each occurrence, is independently selected from the group consisting of alkyl and haloalkyl.

One embodiment of this invention pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (IA)

Formula (IA);

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is C(O)NH, or NHC(O);

Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl;

R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, Cl, and F;

R² is aryl or 5-6 membered heteroaryl wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, SO₂R⁴, OR⁴, and F;

R⁴, at each occurrence, is alkyl or heterocyclyl; wherein each R⁴ alkyl is optionally substituted with R⁷;

R⁷, at each occurrence, is independently heterocyclyl;

wherein the cyclic moieties represented by R⁴ and R⁷ are independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, C(O)R¹⁰, C(O)C(O)R¹⁰, CO(O)R¹⁰, OH and F;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, SO₂R¹¹, NH₂, N(R¹¹)₂, NHC(O)R¹¹, NHS(O)₂R¹¹, OH, NO₂, and F; wherein each R¹⁰ aryl, heterocyclyl and cycloalkyl is optionally substituted with one or more R¹², OR¹², C(O)R¹², OH, CN, CF₃, OCF₃, F, and Cl;

R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹¹ alkyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, C(O)OR¹³, OCF₃, CF₃, F, and Cl;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, and aryl; and

R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, and heterocyclyl;

with the proviso that

when X¹ is CR¹ and X² is CR¹; R¹ is hydrogen; Y¹ is NHC(O); Z¹ is

and R² is pyrrolyl; the R² pyrrolyl is not substituted with two alkyl groups.

Still another embodiment pertains to compounds having Formula (IA), which includes Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658, 659, 660, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672, 673, 674, 675, 676, 677, 678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 688, 689, 690, 691, 692, 693, 694, 695, 696, 697, 698, 699, 700, 701, 702, 703, 704, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716, 717, 718, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747, 748, 749, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, 770, 771, 772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784, 785, 786, 787, 788, 789, 790, 791, 792, 793, 794, 795, 796, 797, 798, 799, 800, 801, 802, 803, 804, 805, 806, 807, 808, 809, 810, 811, 812, 813, 814, 815, 816, 817, 818, 819, 820, 821, 822, 823, 824, 825, 826, 827, 828, 829, 830, 831, 832, 833, 834, 835, 836, 837, 838, 839, 840, 841, 842, 843, 844, 845, 846, 847, 848, 849, 850, 851, 852, 853, 854, 855, 856, 857, 858, 859, 860, 861, 862, 863, 864, 865, 866, 867, 868, 869, 870, 871, 872, and pharmaceutically acceptable salts thereof.

Still another embodiment pertains to compounds of Formula (1A), selected from the group consisting of Examples 147, 310, 313, 316, 317, 320, 332, 333, 334, 402, 433, 440, 658, 681, 691, 706, 707, 723, 736, 795, and pharmaceutically acceptable salts thereof.

Embodiments of Formula (IIA)

In another aspect, the present invention provides compounds of Formula (IIA)

and pharmaceutically acceptable salts thereof; wherein X¹, X², Y¹, R¹, and R² are as described herein for Formula (IA).

One embodiment of this invention pertains to compounds of Formula (IIA) and pharmaceutically acceptable salts thereof;

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is C(O)NH, or NHC(O);

R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I;

R² is independently selected from the group consisting of C₄-C₆-alkyl, C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl, and 5-6 membered heteroaryl; wherein each R² C₄-C₆-alkyl, C₄-C₆-alkenyl, and C₄-C₆-alkynyl is substituted with one or more substituents independently selected from the group consisting of R³, OR³, SR³, S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂, NHR³, N(R³)₂, NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³, NR³C(O)OR³, NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³, NR³C(O)N(R³)₂, C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³, C(O)NHSO₂R³, C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I;

R³, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and heterocyclyl; wherein each R³ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁵, OR⁵, SR⁵, S(O)R⁵, SO₂R⁵, C(O)R⁵, CO(O)R⁵, OC(O)R⁵, OC(O)OR⁵, NH₂, NHR⁵, N(R⁵)₂, NHC(O)R⁵, NR⁵C(O)R⁵, NHS(O)₂R⁵, NR⁵S(O)₂R⁵, NHC(O)OR⁵, NR⁵C(O)OR⁵, NHC(O)NH₂, NHC(O)NHR⁵, NHC(O)N(R⁵)₂, NR⁵C(O)NHR⁵, NR⁵C(O)N(R⁵)₂, C(O)NH₂, C(O)NHR⁵, C(O)N(R⁵)₂, C(O)NHOH, C(O)NHOR⁵, C(O)NHSO₂R⁵, C(O)NR⁵SO₂R⁵, SO₂NH₂, SO₂NHR⁵, SO₂N(R⁵)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁵, C(N)N(R⁵)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R³ aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁶, OR⁶, SR⁶, S(O)R⁶, SO₂R⁶, C(O)R⁶, CO(O)R⁶, OC(O)R⁶, OC(O)OR⁶, NH₂, NHR⁶, N(R⁶)₂, NHC(O)R⁶, NR⁶C(O)R⁶, NHS(O)₂R⁶, NR⁶S(O)₂R⁶, NHC(O)OR⁶, NR⁶C(O)OR⁶, NHC(O)NH₂, NHC(O)NHR⁶, NHC(O)N(R⁶)₂, NR⁶C(O)NHR⁶, NR⁶C(O)N(R⁶)₂, C(O)NH₂, C(O)NHR⁶, C(O)N(R⁶)₂, C(O)NHOH, C(O)NHOR⁶, C(O)NHSO₂R⁶, C(O)NR⁶SO₂R⁶, SO₂NH₂, SO₂NHR⁶, SO₂N(R⁶)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁶, C(N)N(R⁶)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I;

R⁵, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁵ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁸, OR⁸, SR⁸, S(O)R⁸, SO₂R⁸, NHR⁸, N(R⁸)₂, C(O)R⁸, C(O)NH₂, C(O)NHR⁸, C(O)N(R⁸)₂, NHC(O)R⁸, NR⁸C(O)R⁸, NHSO₂R⁸, NHC(O)OR⁸, SO₂NH₂, SO₂NHR⁸, SO₂N(R⁸)₂, NHC(O)NH₂, NHC(O)NHR⁸, OH, (O), C(O)OH, N₃, CN, NH₂, F, Cl, Br and I;

R⁶, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁶ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁹, OR⁹, SR⁹, S(O)R⁹, SO₂R⁹, NHR⁹, N(R⁹)₂, C(O)R⁹, C(O)NH₂, C(O)NHR⁹, C(O)N(R⁹)₂, NHC(O)R⁹, NR⁹C(O)R⁹, NHSO₂R⁹, NHC(O)OR⁹, SO₂NH₂, SO₂NHR⁹, SO₂N(R⁹)₂, NHC(O)NH₂, NHC(O)NHR⁹, OH, (O), C(O)OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br and I;

R⁷, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

R⁸, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

R⁹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

wherein the cyclic moieties represented by R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹ are independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, C(O)C(O)R¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁶SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, CF₃, OCF₃, F, Cl, Br and I;

R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, OR¹³, C(O)OR¹³, OCF₃, CF₃, F, Cl, Br and I;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; and

R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl.

In one embodiment of Formula (IIA), X¹ is N and X² is CR¹; or X¹ is CR¹ and X² is N; or X¹ is CR¹ and X² is CR¹. In another embodiment of Formula (IIA), X¹ is N and X² is CR¹. In another embodiment of Formula (IIA), X¹ is CR¹ and X² is N. In another embodiment of Formula (IIA), X¹ is CR¹ and X² is CR¹.

In one embodiment of Formula (IIA), Y¹ is C(O)NH, or NHC(O). In another embodiment of Formula (IIA), Y¹ is C(O)NH. In another embodiment of Formula (IIA), Y¹ is NHC(O).

In one embodiment of Formula (IIA), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I. In another embodiment of Formula (IIA), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, Cl, Br and I. In another embodiment of Formula (IIA), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, and Cl. In another embodiment of Formula (IIA), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is hydrogen.

In another aspect, the present invention provides compounds of Formula (IIB),

and pharmaceutically acceptable salts thereof; wherein R¹ and R² are as described herein for Formula (IA).

In one embodiment of Formula (IIA) and (IIB), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I. In another embodiment of Formula (IIA) and (IIB), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, Cl, Br and I. In another embodiment of Formula (IIA) and (IIB), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, and Cl. In another embodiment of Formula (IIA) and (IIB), R¹, at each occurrence, is hydrogen.

In one embodiment of Formula (IIA) and (IIB), R² is independently selected from the group consisting of C₄-C₆-alkyl, C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl, and 5-6 membered heteroaryl; wherein each R² C₄-C₆-alkyl, C₄-C₆-alkenyl, and C₄-C₆-alkynyl is substituted with one or more substituents independently selected from the group consisting of R³, OR³, SR³, S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂, NHR³, N(R³)₂, NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³, NR³C(O)OR³, NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³, NR³C(O)N(R³)₂, C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³, C(O)NHSO₂R³, C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I. In another embodiment of Formula (IIA) and (IIB), R² is aryl; wherein each R² aryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, F, Cl, and I. In another embodiment of Formula (IIA) and (IIB), R² is aryl; wherein each R² aryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, and F. In another embodiment of Formula (IIA) and (IIB), R² is phenyl; wherein each R² phenyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, and F. In another embodiment of Formula (IIA) and (IIB), R² is phenyl; wherein each R² phenyl is substituted with one substituent independently selected from the group consisting of R⁴, OR⁴, and SO₂R⁴.

In another embodiment of Formula (IIA) and (IIB), R² is 5-6 membered heteroaryl; wherein each R² 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, F, Cl, and I. In another embodiment of Formula (IIA) and (IIB), R² is 5-6 membered heteroaryl; wherein each R² 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, and F. In another embodiment of Formula (IIA) and (IIB), R² is furanyl or thiophenyl; wherein each R² furanyl and thiophenyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, and F.

In one embodiment of Formula (IIA) and (IIB), R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I. In another embodiment of Formula (IIA) and (IIB), R⁴, at each occurrence, is alkyl or heterocyclyl.

In one embodiment of Formula (IIA) and (IIB), each R⁴ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I. In another embodiment of Formula (I), each R⁴ alkyl is optionally substituted with one R⁷.

In one embodiment of Formula (IIA) and (IIB), R⁷, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl. In another embodiment of Formula (IIA) and (IIB), R⁷, at each occurrence, is heterocyclyl.

In one embodiment of Formula (IIA) and (IIB), each R⁴ and R⁷ heterocyclyl is independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, OR¹³, C(O)OR¹³, OCF₃, CF₃, F, Cl, Br and I; R¹², at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; and R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl.

In another embodiment of Formula (IIA) and (IIB), each R⁴ and R⁷ heterocyclyl is independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, C(O)C(O)R¹⁰, OH, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl, are optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, SO₂R¹¹, NH₂, N(R¹¹)₂, NHC(O)R¹¹, NHS(O)₂R¹¹, OH, NO₂, and F; wherein each R¹⁰ aryl, heterocyclyl and cycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², C(O)R¹², OH, CN, CF₃, OCF₃, F, and Cl; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹¹ alkyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, CF₃, F, and Cl; R¹², at each occurrence, is independently selected from the group consisting of alkyl and aryl; and R¹³, at each occurrence, is independently selected from the group consisting of alkyl and haloalkyl.

One embodiment of this invention pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (IIA)

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is C(O)NH, or NHC(O);

R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, Cl, and F;

R² is aryl or 5-6 membered heteroaryl wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, SO₂R⁴, OR⁴, and F;

R⁴, at each occurrence, is alkyl or heterocyclyl; wherein each R⁴ alkyl is optionally substituted with R⁷;

R⁷, at each occurrence, is independently heterocyclyl;

wherein the cyclic moieties represented by R⁴ and R⁷ are independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, C(O)R¹⁰, C(O)C(O)R¹⁰, CO(O)R¹⁰, OH and F;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, SO₂R¹¹, NH₂, N(R¹¹)₂, NHC(O)R¹¹, NHS(O)₂R¹¹, OH, NO₂, and F; wherein each R¹⁰ aryl, heterocyclyl and cycloalkyl is optionally substituted with one or more R¹², OR¹², C(O)R¹², OH, CN, CF₃, OCF₃, F, and Cl;

R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹¹ alkyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, C(O)OR¹³, OCF₃, CF₃, F, and Cl;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, and aryl; and

R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, and heterocyclyl.

Still another embodiment pertains to compounds having Formula (IIA), which includes Examples 1, 2, 3, 4, 5, 6, 7, 10, 20, 21, 22, 23, 24, 25, 26, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 609, 610, 611, 612, 613, 614, 615, 616, 617, 665, 666, 667, 668, 737, 738, 739, 740, 741, 748, 750, 751, 753, 784, 803, 804, 805, 806, 807, 809, 817, 818, 819, 820, 821, 822, 823, 828, 829, 830, 831, 832, 833, 834, 835, 840, 841, 842, 843, 844, 845, 846, 851, 852, 853, 854, 857, 858, 859, 860, 861, 862, 863, 864, 865, 866, 867, 868, 869, 870, 871, 872, and pharmaceutically acceptable salts thereof.

Embodiments of Formula (IIIA)

In another aspect, the present invention provides compounds of Formula (IIIA)

and pharmaceutically acceptable salts thereof; wherein X¹, X², R¹, and Y¹ are as described in Formula (IA) herein and R^(4x) is as described herein for substituents on R² when R² is aryl in Formula (IA).

One embodiment of this invention pertains to compounds of Formula (IIIA) or pharmaceutically acceptable salts thereof;

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is C(O)NH, or NHC(O);

R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I;

R^(4X) is independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I;

R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I;

R⁷, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

wherein the cyclic moieties represented by R⁴ and R⁷, are independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, C(O)C(O)R¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, CF₃, OCF₃, F, Cl, Br and I;

R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, OR¹³, C(O)OR¹³, OCF₃, CF₃, F, Cl, Br and I;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; and

R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl.

In one embodiment of Formula (IIIA), X¹ is N and X² is CR¹; or X¹ is CR¹ and X² is N; or X¹ is CR¹ and X² is CR¹. In another embodiment of Formula (IIIA), X¹ is N and X² is CR¹. In another embodiment of Formula (IIIA), X¹ is CR¹ and X² is N. In another embodiment of Formula (IIIA), X¹ is CR¹ and X² is CR¹.

In one embodiment of Formula (IIIA), Y¹ is C(O)NH, or NHC(O). In another embodiment of Formula (IIIA), Y¹ is C(O)NH. In another embodiment of Formula (IIIA), Y¹ is NHC(O).

In one embodiment of Formula (IIIA), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I. In another embodiment of Formula (IIIA), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, Cl, Br and I. In another embodiment of Formula (IIIA), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, and Cl. In another embodiment of Formula (IIIA), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is hydrogen.

In another aspect, the present invention provides compounds of Formula (IIIB),

and pharmaceutically acceptable salts thereof; wherein R¹ is described herein for Formula (IA) and R^(4x) is as described herein for substituents on R² when R² is aryl in Formula (IA).

In one embodiment of Formula (IIIA) and (IIIB), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I. In another embodiment of Formula (IIIA) and (IIIB), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, Cl, Br and I. In another embodiment of Formula (IIIA) and (IIIB), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, and Cl. In another embodiment of Formula (IIIA) and (IIIB), R¹, at each occurrence, is hydrogen.

In one embodiment of Formula (IIIA) and (IIIB), R^(4X) is independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I. In another embodiment of Formula (IIIA) and (IIIB), R^(4X) is independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, F, Cl, and I. In another embodiment of Formula (IIIA) and (IIIB), R^(4X) is independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, and F.

In one embodiment of Formula (IIIA) and (IIIB), R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I. In another embodiment of Formula (IIIA) and (IIIB), R⁴, at each occurrence, is alkyl or heterocyclyl.

In one embodiment of Formula (IIIA) and (IIIB), each R⁴ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I. In another embodiment of Formula (IIIA) and (IIIB), each R⁴ alkyl is optionally substituted with one R⁷.

In one embodiment of Formula (IIIA) and (IIIB), R⁷, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl. In another embodiment of Formula (IIIA) and (IIIB), R⁷, at each occurrence, is heterocyclyl.

In one embodiment of Formula (IIIA) and (IIIB), each R⁴ and R⁷ heterocyclyl is independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, OR¹³, C(O)OR¹³, OCF₃, CF₃, F, Cl, Br and I; R¹², at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; and R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl.

In another embodiment of Formula (IIIA) and (IIIB), each R⁴ and R⁷ heterocyclyl is independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, C(O)C(O)R¹⁰, OH, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl, are optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, SO₂R¹¹, NH₂, N(R¹¹)₂, NHC(O)R¹¹, NHS(O)₂R¹¹, OH, NO₂, and F; wherein each R¹⁰ aryl, heterocyclyl and cycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², C(O)R¹², OH, CN, CF₃, OCF₃, F, and Cl; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹¹ alkyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, CF₃, F, and Cl; R¹², at each occurrence, is independently selected from the group consisting of alkyl and aryl; and R¹³, at each occurrence, is independently selected from the group consisting of alkyl and haloalkyl.

One embodiment of this invention pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (IIIA)

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is C(O)NH, or NHC(O);

R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, Cl, and F;

R^(4X) is independently selected from the group consisting of R⁴, SO₂R⁴, OR⁴, and F;

R⁴, at each occurrence, is alkyl or heterocyclyl; wherein each R⁴ alkyl is optionally substituted with R⁷;

R⁷, at each occurrence, is independently heterocyclyl;

wherein the cyclic moieties represented by R⁴ and R⁷ are independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, C(O)R¹⁰, C(O)C(O)R¹⁰, CO(O)R¹⁰, OH and F;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, SO₂R¹¹, NH₂, N(R¹¹)₂, NHC(O)R¹¹, NHS(O)₂R¹¹, OH, NO₂, and F; wherein each R¹⁰ aryl, heterocyclyl and cycloalkyl is optionally substituted with one or more R¹², OR¹², C(O)R¹², OH, CN, CF₃, OCF₃, F, and Cl;

R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹¹ alkyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, C(O)OR¹³, OCF₃, CF₃, F, and Cl;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, and aryl; and

R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, and heterocyclyl.

Still another embodiment pertains to compounds having Formula (IIIA), which includes Examples 1, 2, 3, 4, 5, 6, 7, 10, 20, 22, 25, 26, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 609, 610, 611, 612, 613, 614, 615, 616, 617, 665, 666, 667, 668, 737, 738, 739, 740, 741, 748, 750, 751, 753, 784, 803, 804, 805, 806, 807, 809, 817, 818, 819, 820, 821, 822, 823, 840, 841, 842, 843, 844, 845, 846, 851, 852, 853, 854, 857, 863, 864, 865, 866, 867, and pharmaceutically acceptable salts thereof.

Embodiments of Formula (IVA)

In another aspect, the present invention provides compounds of Formula (IVA)

and pharmaceutically acceptable salts thereof; wherein each X¹, X², Y¹, R¹, and R² are as described herein for Formula (I).

One embodiment of this invention pertains to compounds of Formula (IVA) and pharmaceutically acceptable salts thereof;

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is C(O)NH, or NHC(O);

R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I;

R² is independently selected from the group consisting of C₄-C₆-alkyl, C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl, and 5-6 membered heteroaryl; wherein each R² C₄-C₆-alkyl, C₄-C₆-alkenyl, and C₄-C₆-alkynyl is substituted with one or more substituents independently selected from the group consisting of R³, OR³, SR³, S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂, NHR³, N(R³)₂, NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³, NR³C(O)OR³, NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³, NR³C(O)N(R³)₂, C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³, C(O)NHSO₂R³, C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I;

R³, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and heterocyclyl; wherein each R³ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁵, OR⁵, SR⁵, S(O)R⁵, SO₂R⁵, C(O)R⁵, CO(O)R⁵, OC(O)R⁵, OC(O)OR⁵, NH₂, NHR⁵, N(R⁵)₂, NHC(O)R⁵, NR⁵C(O)R⁵, NHS(O)₂R⁵, NR⁵S(O)₂R⁵, NHC(O)OR⁵, NR⁵C(O)OR⁵, NHC(O)NH₂, NHC(O)NHR⁵, NHC(O)N(R⁵)₂, NR⁵C(O)NHR⁵, NR⁵C(O)N(R⁵)₂, C(O)NH₂, C(O)NHR⁵, C(O)N(R⁵)₂, C(O)NHOH, C(O)NHOR⁵, C(O)NHSO₂R⁵, C(O)NR⁵SO₂R⁵, SO₂NH₂, SO₂NHR⁵, SO₂N(R⁵)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁵, C(N)N(R⁵)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R³ aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁶, OR⁶, SR⁶, S(O)R⁶, SO₂R⁶, C(O)R⁶, CO(O)R⁶, OC(O)R⁶, OC(O)OR⁶, NH₂, NHR⁶, N(R⁶)₂, NHC(O)R⁶, NR⁶C(O)R⁶, NHS(O)₂R⁶, NR⁶S(O)₂R⁶, NHC(O)OR⁶, NR⁶C(O)OR⁶, NHC(O)NH₂, NHC(O)NHR⁶, NHC(O)N(R⁶)₂, NR⁶C(O)NHR⁶, NR⁶C(O)N(R⁶)₂, C(O)NH₂, C(O)NHR⁶, C(O)N(R⁶)₂, C(O)NHOH, C(O)NHOR⁶, C(O)NHSO₂R⁶, C(O)NR⁶SO₂R⁶, SO₂NH₂, SO₂NHR⁶, SO₂N(R⁶)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁶, C(N)N(R⁶)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I;

R⁵, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁵ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁸, OR⁸, SR⁸, S(O)R⁸, SO₂R⁸, NHR⁸, N(R⁸)₂, C(O)R⁸, C(O)NH₂, C(O)NHR⁸, C(O)N(R⁸)₂, NHC(O)R⁸, NR⁸C(O)R⁸, NHSO₂R⁸, NHC(O)OR⁸, SO₂NH₂, SO₂NHR⁸, SO₂N(R⁸)₂, NHC(O)NH₂, NHC(O)NHR⁸, OH, (O), C(O)OH, N₃, CN, NH₂, F, Cl, Br and I;

R⁶, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁶ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁹, OR⁹, SR⁹, S(O)R⁹, SO₂R⁹, NHR⁹, N(R⁹)₂, C(O)R⁹, C(O)NH₂, C(O)NHR⁹, C(O)N(R⁹)₂, NHC(O)R⁹, NR⁹C(O)R⁹, NHSO₂R⁹, NHC(O)OR⁹, SO₂NH₂, SO₂NHR⁹, SO₂N(R⁹)₂, NHC(O)NH₂, NHC(O)NHR⁹, OH, (O), C(O)OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br and I;

R⁷, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

R⁸, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

R⁹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

wherein the cyclic moieties represented by R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹ are independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, C(O)C(O)R¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, CF₃, OCF₃, F, Cl, Br and I;

R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, OR¹³, C(O)OR¹³, OCF₃, CF₃, F, Cl, Br and I;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; and

R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

with the proviso that when X¹ is CR¹ and X² is CR¹; R¹ is hydrogen; Y¹ is NHC(O); and R² is pyrrolyl; the R² pyrrolyl is not substituted with two alkyl groups.

In one embodiment of Formula (IVA), X¹ is N and X² is CR¹; or X¹ is CR¹ and X² is N; or X¹ is CR¹ and X² is CR¹. In another embodiment of Formula (IVA), X¹ is N and X² is CR¹. In another embodiment of Formula (IVA), X¹ is CR¹ and X² is N. In another embodiment of Formula (IVA), X¹ is CR¹ and X² is CR¹.

In one embodiment of Formula (IVA), Y¹ is C(O)NH, or NHC(O). In another embodiment of Formula (IVA), Y¹ is C(O)NH. In another embodiment of Formula (IVA), Y¹ is NHC(O).

In one embodiment of Formula (IVA), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I. In another embodiment of Formula (IVA), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, Cl, Br and I. In another embodiment of Formula (IVA), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, and Cl. In another embodiment of Formula (IVA), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is hydrogen.

In another aspect, the present invention provides compounds of Formula (IVB),

and pharmaceutically acceptable salts thereof; wherein R¹ and R² are as described herein for Formula (IA).

In one embodiment of Formula (IVA) and (IVB), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I. In another embodiment of Formula (IVA) and (IVB), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, Cl, Br and I. In another embodiment of Formula (IVA) and (IVB), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, and Cl. In another embodiment of Formula (IVA) and (IVB), R¹, at each occurrence, is hydrogen.

In one embodiment of Formula (IVA) and (IVB), R² is independently selected from the group consisting of C₄-C₆-alkyl, C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl, and 5-6 membered heteroaryl; wherein each R² C₄-C₆-alkyl, C₄-C₆-alkenyl, and C₄-C₆-alkynyl is substituted with one or more substituents independently selected from the group consisting of R³, OR³, SR³, S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂, NHR³, N(R³)₂, NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³, NR³C(O)OR³, NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³, NR³C(O)N(R³)₂, C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³, C(O)NHSO₂R³, C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I. In another embodiment of Formula (IVA) and (IVB), R² is aryl; wherein each R² aryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, F, Cl, and I. In another embodiment of Formula (IVA) and (IVB), R² is aryl; wherein each R² aryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, and F. In another embodiment of Formula (IVA) and (IVB), R² is phenyl; wherein each R² phenyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, and F. In another embodiment of Formula (IVA) and (IVB), R² is phenyl; wherein each R² phenyl is substituted with one substituent independently selected from the group consisting of R⁴, OR⁴, and SO₂R⁴.

In another embodiment of Formula (IVA) and (IVB), R² is 5-6 membered heteroaryl; wherein each R² 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, F, Cl, and I. In another embodiment of Formula (IVA) and (IVB), R² is 5-6 membered heteroaryl; wherein each R² 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, and F. In another embodiment of Formula (IVA) and (IVB), R² is furanyl or thiophenyl; wherein each R² furanyl and thiophenyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, and F.

In one embodiment of Formula (IVA) and (IVB), R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)R⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I. In another embodiment of Formula (IVA) and (IVB), R⁴, at each occurrence, is alkyl or heterocyclyl.

In one embodiment of Formula (IVA) and (IVB), each R⁴ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I. In another embodiment of Formula (IVA) and (IVB), each R⁴ alkyl is optionally substituted with one R⁷.

In one embodiment of Formula (IVA) and (IVB), R⁷, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl. In another embodiment of Formula (IVA) and (IVB), R⁷, at each occurrence, is heterocyclyl.

In one embodiment of Formula (IVA) and (IVB), each R⁴ and R⁷ heterocyclyl is independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, OR¹³, C(O)OR¹³, OCF₃, CF₃, F, Cl, Br and I; R¹², at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; and R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl.

In another embodiment of Formula (IVA) and (IVB), each R⁴ and R⁷ heterocyclyl is independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, C(O)C(O)R¹⁰, OH, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl, are optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, SO₂R¹¹, NH₂, N(R¹¹)₂, NHC(O)R¹¹, NHS(O)₂R¹¹, OH, NO₂, and F; wherein each R¹⁰ aryl, heterocyclyl and cycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², C(O)R¹², OH, CN, CF₃, OCF₃, F, and Cl; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹¹ alkyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, CF₃, F, and Cl; R¹², at each occurrence, is independently selected from the group consisting of alkyl and aryl; and R¹³, at each occurrence, is independently selected from the group consisting of alkyl and haloalkyl.

One embodiment of this invention pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (IVA)

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is C(O)NH, or NHC(O);

R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, Cl, and F;

R² is aryl or 5-6 membered heteroaryl wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, SO₂R⁴, OH, and F;

R⁴, at each occurrence, is alkyl or heterocyclyl; wherein each R⁴ alkyl is optionally substituted with R⁷;

R⁷, at each occurrence, is independently heterocyclyl;

wherein the cyclic moieties represented by R⁴ and R⁷ are independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, C(O)R¹⁰, C(O)C(O)R¹⁰, CO(O)R¹⁰, OH and F;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, SO₂R¹¹, NH₂, N(R¹¹)₂, NHC(O)R¹¹, NHS(O)₂R¹¹, OH, NO₂, and F; wherein each R¹⁰ aryl, heterocyclyl and cycloalkyl is optionally substituted with one or more R¹², OR¹², C(O)R¹², OH, CN, CF₃, OCF₃, F, and Cl;

R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹¹ alkyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, C(O)OR¹³, OCF₃, CF₃, F, and Cl;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, and aryl; and

R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, and heterocyclyl;

with the proviso that when X¹ is CR¹ and X² is CR¹; R¹ is hydrogen; Y¹ is NHC(O); and R² is pyrrolyl; the R² pyrrolyl is not substituted with two alkyl groups.

Still another embodiment pertains to compounds having Formula (IVA), which includes Examples 8, 9, 11, 12, 13, 14, 15, 16, 17, 18, 19, 27, 28, 141, 142, 204, 310, 311, 312, 313, 614, 615, 616, 617, 618, 619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658, 659, 660, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672, 673, 674, 675, 676, 677, 678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 688, 689, 690, 691, 692, 693, 694, 695, 696, 697, 698, 699, 700, 701, 702, 703, 704, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716, 717, 718, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747, 748, 749, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, 770, 771, 772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784, 785, 786, 787, 788, 789, 790, 791, 792, 793, 794, 795, 796, 797, 798, 799, 800, 801, 802, 803, 804, 805, 806, 807, 808, 809, 810, 811, 812, 813, 814, 815, 816, 817, 818, 819, 820, 821, 822, 823, 824, 825, 826, 827, 828, 829, 830, 831, 832, 833, 834, 835, 836, 837, 838, 839, 840, 841, 842, 843, 844, 845, 846, 847, 848, 849, 850, 851, 852, 853, 854, 855, 856, 857, 858, 859, 860, 861, 862, 863, 864, 865, 866, 867, 868, 869, 870, 871, 872, and pharmaceutically acceptable salts thereof.

Embodiments of Formula (VA)

In another aspect, the present invention provides compounds of Formula (VA)

and pharmaceutically acceptable salts thereof; wherein X¹, X², R¹, and Y¹ are as described in Formula (IA) herein and R^(4x) is as described herein for substituents on R² when R² is aryl in Formula (IA).

One embodiment of this invention pertains to compounds of Formula (VA) or pharmaceutically acceptable salts thereof;

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is C(O)NH, or NHC(O);

R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I;

R^(4X) is independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I;

R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I;

R⁷, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

wherein the cyclic moieties represented by R⁴, and R⁷, are independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, C(O)C(O)R¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, CF₃, OCF₃, F, Cl, Br and I;

R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, OR¹³, C(O)OR¹³, OCF₃, CF₃, F, Cl, Br and I;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; and

R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl.

In one embodiment of Formula (VA), X¹ is N and X² is CR¹; or X¹ is CR¹ and X² is N; or X¹ is CR¹ and X² is CR¹. In another embodiment of Formula (VA), X¹ is N and X² is CR¹. In another embodiment of Formula (VA), X¹ is CR¹ and X² is N. In another embodiment of Formula (VA), X¹ is CR¹ and X² is CR¹.

In one embodiment of Formula (VA), Y¹ is C(O)NH, or NHC(O). In another embodiment of Formula (VA), Y¹ is C(O)NH. In another embodiment of Formula (VA), Y¹ is NHC(O).

In one embodiment of Formula (VA), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I. In another embodiment of Formula (VA), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, Cl, Br and I. In another embodiment of Formula (VA), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, and Cl. In another embodiment of Formula (VA), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is hydrogen.

In another aspect, the present invention provides compounds of Formula (VB),

and pharmaceutically acceptable salts thereof; wherein R¹ is described herein for Formula (IA) and R^(4x) is as described herein for substituents on R² when R² is aryl in Formula (IA).

In one embodiment of Formula (VA) and (VB), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I. In another embodiment of Formula (VA) and (VB), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, Cl, Br and I. In another embodiment of Formula (VA) and (VB), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, and Cl. In another embodiment of Formula (VA) and (VB), R¹, at each occurrence, is hydrogen.

In one embodiment of Formula (VA) and (VB), R^(4X) is independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I. In another embodiment of Formula (VA) and (VB), R^(4X) is independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, F, Cl, and I. In another embodiment of Formula (VA) and (VB), R^(4X) is independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, and F.

In one embodiment of Formula (VA) and (VB), R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I. In another embodiment of Formula (VA) and (VB), R⁴, at each occurrence, is alkyl or heterocyclyl.

In one embodiment of Formula (VA) and (VB), each R⁴ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I. In another embodiment of Formula (I), each R⁴ alkyl is optionally substituted with one R⁷.

In one embodiment of Formula (VA) and (VB), R⁷, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl. In another embodiment of Formula (VA) and (VB), R⁷, at each occurrence, is heterocyclyl.

In one embodiment of Formula (VA) and (VB), each R⁴ and R⁷ heterocyclyl is independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, OR¹³, C(O)OR¹³, OCF₃, CF₃, F, Cl, Br and I; R¹², at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; and R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl.

In another embodiment of Formula (VA) and (VB), each R⁴ and R⁷ heterocyclyl is independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, C(O)C(O)R¹⁰, OH, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl, are optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, SO₂R¹¹, NH₂, N(R¹¹)₂, NHC(O)R¹¹, NHS(O)₂R¹¹, OH, NO₂, and F; wherein each R¹⁰ aryl, heterocyclyl and cycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹² OR¹², C(O)R¹², OH, CN, CF₃, OCF₃, F, and Cl; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹¹ alkyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, CF₃, F, and Cl; R¹², at each occurrence, is independently selected from the group consisting of alkyl and aryl; and R¹³, at each occurrence, is independently selected from the group consisting of alkyl and haloalkyl.

One embodiment of this invention pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (VA)

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is C(O)NH, or NHC(O);

R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, Cl, and F;

R^(4X) is independently selected from the group consisting of R⁴, SO₂R⁴, OR⁴, and F;

R⁴, at each occurrence, is alkyl or heterocyclyl; wherein each R⁴ alkyl is optionally substituted with R⁷;

R⁷, at each occurrence, is independently heterocyclyl;

wherein the cyclic moieties represented by R⁴ and R⁷ are independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, C(O)R¹⁰, C(O)C(O)R¹⁰, CO(O)R¹⁰, OH and F;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, SO₂R¹¹, NH₂, N(R¹¹)₂, NHC(O)R¹¹, NHS(O)₂R¹¹, OH, NO₂, and F; wherein each R¹⁰ aryl, heterocyclyl and cycloalkyl is optionally substituted with one or more R¹², OR¹², C(O)R¹², OH, CN, CF₃, OCF₃, F, and Cl;

R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹¹ alkyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, C(O)OR¹³, OCF₃, CF₃, F, and Cl;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, and aryl; and

R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, and heterocyclyl.

Still another embodiment pertains to compounds having Formula (VA), which includes Examples 8, 9, 11, 12, 13, 14, 15, 16, 17, 18, 19, 27, 28, 141, 142, 204, 310, 311, 312, 313, 614, 615, 616, 617, 625, 626, 627, 628, 630, 631, 632, 633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658, 659, 660, 661, 662, 663, 665, 666, 667, 668, 669, 670, 671, 672, 673, 674, 675, 676, 677, 678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 688, 689, 690, 691, 692, 693, 694, 695, 696, 697, 698, 699, 700, 701, 702, 703, 704, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716, 717, 718, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 743, 744, 745, 748, 749, 750, 751, 752, 753, 756, 757, 759, 769, 770, 771, 772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784, 785, 786, 787, 788, 789, 790, 791, 792, 793, 794, 795, 796, 797, 798, 799, 800, 801, 802, 803, 804, 805, 806, 807, 808, 809, 810, 811, 812, 813, 814, 815, 816, 817, 818, 819, 820, 821, 822, 823, 824, 825, 826, 827, 828, 829, 830, 831, 832, 833, 834, 835, 836, 837, 838, 839, 840, 841, 842, 843, 844, 845, 846, 847, 848, 849, 850, 851, 852, 853, 854, 855, 856, 857, 858, 859, 860, 861, 862, 863, 864, 865, 866, 867, 868, 869, 870, 871, 872, and pharmaceutically acceptable salts thereof.

Embodiments of Formula (IC)

One embodiment of this invention, therefore, pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (IC)

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is C(O)NH, or NHC(O);

Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl;

R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I;

R² is independently selected from the group consisting of C₄-C₆-alkyl, C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl, and 5-6 membered heteroaryl; wherein each R² C₄-C₆-alkyl, C₄-C₆-alkenyl, and C₄-C₆-alkynyl is substituted with one or more substituents independently selected from the group consisting of R³, OR³, SR³, S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂, NHR³, N(R³)₂, NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³, NR³C(O)OR³, NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³, NR³C(O)N(R³)₂, C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³, C(O)NHSO₂R³, C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I;

R³, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and heterocyclyl; wherein each R³ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁵, OR⁵, SR⁵, S(O)R⁵, SO₂R⁵, C(O)R⁵, CO(O)R⁵, OC(O)R⁵, OC(O)OR⁵, NH₂, NHR⁵, N(R⁵)₂, NHC(O)R⁵, NR⁵C(O)R⁵, NHS(O)₂R⁵, NR⁵S(O)₂R⁵, NHC(O)OR⁵, NR⁵C(O)OR⁵, NHC(O)NH₂, NHC(O)NHR⁵, NHC(O)N(R⁵)₂, NR⁵C(O)NHR⁵, NR⁵C(O)N(R⁵)₂, C(O)NH₂, C(O)NHR⁵, C(O)N(R⁵)₂, C(O)NHOH, C(O)NHOR⁵, C(O)NHSO₂R⁵, C(O)NR⁵SO₂R⁵, SO₂NH₂, SO₂NHR⁵, SO₂N(R⁵)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁵, C(N)N(R⁵)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R³ aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁶, OR⁶, SR⁶, S(O)R⁶, SO₂R⁶, C(O)R⁶, CO(O)R⁶, OC(O)R⁶, OC(O)OR⁶, NH₂, NHR⁶, N(R⁶)₂, NHC(O)R⁶, NR⁶C(O)R⁶, NHS(O)₂R⁶, NR⁶S(O)₂R⁶, NHC(O)OR⁶, NR⁶C(O)OR⁶, NHC(O)NH₂, NHC(O)NHR⁶, NHC(O)N(R⁶)₂, NR⁶C(O)NHR⁶, NR⁶C(O)N(R⁶)₂, C(O)NH₂, C(O)NHR⁶, C(O)N(R⁶)₂, C(O)NHOH, C(O)NHOR⁶, C(O)NHSO₂R⁶, C(O)NR⁶SO₂R⁶, SO₂NH₂, SO₂NHR⁶, SO₂N(R⁶)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁶, C(N)N(R⁶)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I;

R⁵, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁵ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁸, OR⁸, SR⁸, S(O)R⁸, SO₂R⁸, NHR⁸, N(R⁸)₂, C(O)R⁸, C(O)NH₂, C(O)NHR⁸, C(O)N(R⁸)₂, NHC(O)R⁸, NR⁸C(O)R⁸, NHSO₂R⁸, NHC(O)OR⁸, SO₂NH₂, SO₂NHR⁸, SO₂N(R⁸)₂, NHC(O)NH₂, NHC(O)NHR⁸, OH, (O), C(O)OH, N₃, CN, NH₂, F, Cl, Br and I;

R⁶, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁶ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁹, OR⁹, SR⁹, S(O)R⁹, SO₂R⁹, NHR⁹, N(R⁹)₂, C(O)R⁹, C(O)NH₂, C(O)NHR⁹, C(O)N(R⁹)₂, NHC(O)R⁹, NR⁹C(O)R⁹, NHSO₂R⁹, NHC(O)OR⁹, SO₂NH₂, SO₂NHR⁹, SO₂N(R⁹)₂, NHC(O)NH₂, NHC(O)NHR⁹, OH, (O), C(O)OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br and I;

R⁷, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

R⁸, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

R⁹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

wherein the cyclic moieties represented by R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹ are independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, C(O)C(O)R¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁶SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, CF₃, OCF₃, F, Cl, Br and I;

R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, OR¹³, C(O)OR¹³, OCF₃, CF₃, F, Cl, Br and I;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; and

R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

with the proviso that when X¹ is CR¹ and X² is CR¹; R¹ is hydrogen; Y¹ is NHC(O); Z¹ is

and R² is pyrrolyl; the R² pyrrolyl is not substituted with two alkyl groups.

In one embodiment of Formula (IC), X¹ is N and X² is CR¹; or X¹ is CR¹ and X² is N; or X¹ is CR¹ and X² is CR¹. In another embodiment of Formula (IC), X¹ is N and X² is CR¹. In another embodiment of Formula (IC), X¹ is CR¹ and X² is N. In another embodiment of Formula (IC), X¹ is CR¹ and X² is CR¹.

In one embodiment of Formula (IC), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I. In another embodiment of Formula (IC), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, Cl, Br and I. In another embodiment of Formula (IC), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, and Cl. In another embodiment of Formula (IC), R¹, at each occurrence, is hydrogen.

In one embodiment of Formula (IC), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I. In another embodiment of Formula (IC), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, Cl, Br and I. In another embodiment of Formula (IC), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, and Cl. In another embodiment of Formula (IC), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is hydrogen.

In one embodiment of Formula (IC), Y¹ is C(O)NH, or NHC(O). In another embodiment of Formula (IC), Y¹ is C(O)NH. In another embodiment of Formula (IC), Y¹ is NHC(O).

In one embodiment of Formula (IC), Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl. In another embodiment of Formula (IC), Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl. In another embodiment of Formula (IC), Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl. In another embodiment of Formula (IC), Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl. In another embodiment of Formula (IC), Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl.

In one embodiment of Formula (IC), R² is independently selected from the group consisting of C₄-C₆-alkyl, C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl, and 5-6 membered heteroaryl; wherein each R² C₄-C₆-alkyl, C₄-C₆-alkenyl, and C₄-C₆-alkynyl is substituted with one or more substituents independently selected from the group consisting of R³, OR³, SR³, S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂, NHR³, N(R³)₂, NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³, NR³C(O)OR³, NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³, NR³C(O)N(R³)₂, C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³, C(O)NHSO₂R³, C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I. In another embodiment of Formula (IC), R² is aryl; wherein each R² aryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, C(O)NHR⁴, F, Cl, and I. In another embodiment of Formula (IC), R² is aryl; wherein each R² aryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, C(O)NHR⁴, and F. In another embodiment of Formula (IC), R² is phenyl; wherein each R² phenyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, C(O)NHR⁴, and F. In another embodiment of Formula (IC), R² is phenyl; wherein each R² phenyl is substituted with one substituent independently selected from the group consisting of R⁴, OR⁴, and SO₂R⁴.

In another embodiment of Formula (IC), R² is 5-6 membered heteroaryl; wherein each R² 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, C(O)NHR⁴, F, Cl, and I. In another embodiment of Formula (IC), R² is 5-6 membered heteroaryl; wherein each R² 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, C(O)NHR⁴, and F. In another embodiment of Formula (IC), R² is pyridinyl, furanyl, thiophenyl, pyrazole, or thiazolyl; wherein each R² pyridinyl, furanyl, thiophenyl, pyrazole, and thiazolyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, C(O)NHR⁴, and F.

In one embodiment of Formula (IC), R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I. In another embodiment of Formula (IC), R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl.

In one embodiment of Formula (IC), each R⁴ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I. In another embodiment of Formula (IC), each R⁴ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, N(R⁷)₂, F, Cl, Br and I.

In one embodiment of Formula (IC), R⁷, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl. In another embodiment of Formula (IC), R⁷, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl.

In one embodiment of Formula (IC), each R⁴ and R⁷ cyclic moiety is independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂ NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, OR¹³, C(O)OR¹³, OCF₃, CF₃, F, Cl, Br and I; R¹², at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; and R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl.

In another embodiment of Formula (IC), each R⁴ and R⁷ cyclic moiety is independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, C(O)C(O)R¹⁰, CO(O)H, OH, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl, are optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, SO₂R¹¹, NH₂, N(R¹¹)₂, NHC(O)R¹¹, NHS(O)₂R¹¹, OH, NO₂, and F; wherein each R¹⁰ aryl, heterocyclyl and cycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², C(O)R¹², NH₂, OH, CN, CF₃, OCF₃, F, and Cl; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹¹ alkyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, CF₃, F, and Cl; R¹², at each occurrence, is independently selected from the group consisting of alkyl and aryl; and R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, and cycloalkyl.

One embodiment of this invention pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (IC)

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is C(O)NH, or NHC(O);

Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl;

R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, Cl, and F;

R² is aryl or 5-6 membered heteroaryl wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, SO₂R⁴, OR⁴, C(O)NHR⁴, and F;

R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, and cycloalkyl; wherein each R⁴ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, N(R⁷)₂, and F;

R⁷, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl;

wherein the cyclic moieties represented by R⁴ and R⁷ are independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, C(O)R¹⁰, C(O)C(O)R¹⁰, CO(O)OH, OH and F;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, SO₂R¹¹, NH₂, N(R¹¹)₂, N(R)¹¹, NHC(O)R¹¹, NHS(O)₂R¹¹, OH, NO₂, and F; wherein each R¹⁰ aryl, heterocyclyl and cycloalkyl is optionally substituted with one or more R¹², OR¹², C(O)R¹², NH₂, OH, CN, CF₃, OCF₃, F, and Cl;

R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹¹ alkyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, C(O)OR¹³, OCF₃, CF₃, F, and Cl;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, and aryl; and

R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, cycloalkyl, and heterocyclyl;

with the proviso that

when X¹ is CR¹ and X² is CR¹; R¹ is hydrogen; Y¹ is NHC(O); Z¹ is

and R² is pyrrolyl; the R² pyrrolyl is not substituted with two alkyl groups.

Still another embodiment pertains to compounds having Formula (IC), which include

-   1-(pyridin-3-yl)-N-(4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy     phenyl)azetidine-3-carboxamide; -   1-(2-cyanopyridin-3-yl)-N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)-1-[2-(trifluoromethyl)pyridin-3-yl]azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(4-methylpyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(4-fluoropyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)-1-[4-(trifluoromethyl)pyridin-3-yl]azetidine-3-carboxamide; -   tert-butyl     4-[4-({[(3S)-1-(pyridin-3-yl)pyrrolidin-3-yl]carbonyl}amino)phenoxy]piperidine-1-carboxylate; -   tert-butyl     4-[4-({[(3R)-1-(pyridin-3-yl)pyrrolidin-3-yl]carbonyl}amino)phenoxy]piperidine-1-carboxylate; -   1-(pyridin-3-yl)-N-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   (3S)-1-(pyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridin-3-yl)-N-[4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]pyrrolidine-3-carboxamide; -   (3S)-1-(pyridin-3-yl)-N-[4-({1-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]pyrrolidine-3-carboxamide; -   (3S)-1-(pyridin-3-yl)-N-(4-{[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridin-3-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxy}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}     oxy)phenyl]-1-(pyridin-3-yl)pyrrolidine-3-carboxamide; -   N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[1-(pyridin-3-yl)azetidin-3-yl]-4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}benzamide; -   N-(4-{1-[(2S)-2-methylbutanoyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)-N-[1-(pyridin-3-yl)azetidin-3-yl]benzamide; -   4-{[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]oxy}-N-[1-(pyridin-3-yl)azetidin-3-yl]benzamide; -   1-(pyridin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   tert-butyl     4-(4-{[(3S)-1-(pyridin-3-yl)pyrrolidin-3-yl]carbamoyl}phenoxy)piperidine-1-carboxylate; -   tert-butyl     4-(4-{[(3R)-1-(pyridin-3-yl)pyrrolidin-3-yl]carbamoyl}phenoxy)piperidine-1-carboxylate; -   N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-[4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-{4-[(1-pentanoylpiperidin-4-yl)oxy]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-methylpentanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylpentanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-ethoxypropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3,3-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-butanoylpiperidin-4-yl)oxy]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(ethoxyacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(N-acetyl-L-leucyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclohexylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclohexylacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-(4-{[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1-methylcyclohexyl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(furan-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide;     1-(pyridin-3-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-{4-[(1-acetylpiperidin-4-yl)oxy]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(methoxyacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide;     1-(pyridin-3-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(morpholin-4-ylacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(furan-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide;     N-[4-({1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-propanoylpiperidin-4-yl)oxy]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(N,N-dimethyl-beta-alanyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-(4-{[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,3-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(4-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(2-methoxypyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylmethyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpentyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylbutyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-ethylbutyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylpropyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylbutyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-propylpiperidin-4-yl)oxy]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-cyclopropylethyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-(4-{[1-(tetrahydrofuran-3-ylmethyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylbutyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclohexylmethyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopentylmethyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylbutyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylpentyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-butylpiperidin-4-yl)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-ethylbutyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylbutyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylpropyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-propylpiperidin-4-yl)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(4-methoxypyridin-3-yl)azetidine-3-carboxamide; -   1-(4-cyanopyridin-3-yl)-N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-[4-(1-pentanoylpiperidin-4-yl)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(morpholin-4-ylacetyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(furan-3-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-{4-[1-(pyrrolidin-1-ylacetyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(5-oxo-D-prolyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(N,N-dimethyl-beta-alanyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-{4-[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(4-methylpiperazin-1-yl)acetyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(5-oxo-L-prolyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-ethoxypropanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(1-methylcyclohexyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-acetylpiperidin-4-yl)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclohexylacetyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(N-acetyl-L-leucyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-propanoylpiperidin-4-yl)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[3-(morpholin-4-yl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(furan-2-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[3-(piperidin-1-yl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(ethoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-butanoylpiperidin-4-yl)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclohexylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopentylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   (3S)—N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)pyrrolidine-3-carboxamide; -   N-(4-{1-[(2S)-2-methylbutanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,5-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-(4-{1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(pyridazin-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-[4-(1-pentanoylpiperidin-4-yl)phenyl]azetidine-3-carboxamide; -   N-{4-[1-(3-methylpentanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]piperidin-4-yl}phenyl)-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(morpholin-4-ylacetyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(furan-3-ylcarbonyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(pyrrolidin-1-ylacetyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(5-oxo-D-prolyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(N,N-dimethyl-beta-alanyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-(4-{1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(4-methylpiperazin-1-yl)acetyl]piperidin-4-yl}phenyl)-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(5-oxo-L-prolyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(3-ethoxypropanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-methylpentanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(1-methylcyclohexyl)carbonyl]piperidin-4-yl}phenyl)-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-acetylpiperidin-4-yl)phenyl]-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclohexylacetyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(N-acetyl-L-leucyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-[4-(1-propanoylpiperidin-4-yl)phenyl]azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}phenyl)-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-(4-{1-[3-(morpholin-4-yl)propanoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-(4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(furan-2-ylcarbonyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-(4-{1-[3-(piperidin-1-yl)propanoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(ethoxyacetyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-butanoylpiperidin-4-yl)phenyl]-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclohexylcarbonyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-fluorobenzoyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,4-difluorobenzoyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({1-[difluoro(phenyl)acetyl]azetidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({1-[(4,4-difluoro     cyclohexyl)carbonyl]azetidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({1-[(4-fluorophenyl)acetyl]azetidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)pyrrolidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({1-[4-(trifluoromethyl)benzoyl]azetidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-{4-[(1-benzoylazetidin-3-yl)oxy]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-hydroxy-2-methylpropanoyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydrofuran-3-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(furan-3-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[(1-pentanoylazetidin-3-yl)oxy]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[difluoro(phenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methyl-2-phenylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(1,3-thiazol-4-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[(1-{[4-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)oxy]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({1[3-(trifluoromethyl)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({1[3-(trifluoromethoxy)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-(4-{[1-(3-methylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(3-fluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,4-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(4-fluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3,4-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({1-[4-(trifluoromethoxy)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-[4-({1-[(2,4-difluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[(1-{[4-(trifluoromethoxy)phenyl]acetyl}piperidin-4-yl)oxy]phenyl}azetidine-3-carboxamide; -   N-[4-({1-[(3,5-difluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[(1-{[3-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)oxy]phenyl}azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(pyridin-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(3,5-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-acetylpiperidin-4-yl)oxy]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(methoxyacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2-fluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(3-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3,3-dimethylbutanoyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclohexylcarbonyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(2-methylcyclopropyl)carbonyl]azetidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)azetidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylcarbonyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3,3-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclobutylcarbonyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydrofuran-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(4-methylpentanoyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropanoyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2S)-2-methylbutanoyl]azetidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(methoxyacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[difluoro(phenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({1-[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(1,3-thiazol-4-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[(1-{[4-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)oxy]phenyl}azetidine-3-carboxamide; -   N-(4-{[1-(3,4-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[(1-{[4-(trifluoromethoxy)phenyl]acetyl}piperidin-4-yl)oxy]phenyl}azetidine-3-carboxamide; -   N-[4-({1-[(4-fluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide;     N-[4-({1-[(2,4-difluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(2-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methyl-2-phenylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[(1-acetylpiperidin-4-yl)oxy]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(2,4-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({1-[3-(trifluoromethyl)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-(4-{[1-(3-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-[4-({1-[(3-fluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({1-[4-(trifluoromethoxy)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-[4-({1-[(3,5-difluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({1[3-(trifluoromethoxy)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(pyridin-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(4-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(3,5-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[(1-{[3-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)oxy]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2-fluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]furan-2-carboxamide; -   (3S)—N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   tert-butyl     4-(4-{[1-(pyridazin-3-yl)azetidin-3-yl]carbamoyl}phenyl)piperidine-1-carboxylate; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   N-[4-(1-acetylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-butanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-pentanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-hexanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-ethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-heptanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(but-3-enoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(p     ent-4-enoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(methylsulfanyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-nitropropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[3-(methylsulfanyl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(pent-4-ynoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclohexylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclohexylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-hydroxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-hydroxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-hydroxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methoxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methoxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-methoxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-cyanobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-cyanobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{1-[3-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{1-[3-(trifluoromethoxy)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(2,3-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,4-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,5-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,4-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,5-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,4-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,5-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,4-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,5-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(3-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(4-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2-chlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(4-chlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-(1-{[4-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)phenyl]azetidine-3-carboxamide; -   N-(4-{1-[(3,5-dimethylphenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2,5-difluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(3,4-dichlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(furan-3-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(5-methylpyrazin-2-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-ethoxypropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(1-phenylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{1-[(pyrimidin-2-ylsulfanyl)acetyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-(4-{1-[(1-acetylpiperidin-4-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(3,5-difluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(N-acetyl-L-leucyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(diphenylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-fluoro-2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(5-fluoro-2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-fluoro-4-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,3-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[4-(propan-2-yl)benzoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-tert-butylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[2-fluoro-5-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[2-chloro-5-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(4-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(4-methylphenoxy)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2S)-2-phenylbutanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-(1-{[3-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)phenyl]azetidine-3-carboxamide; -   N-(4-{1-[(3-chlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2,4-dichlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(naphthalen-1-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2R)-2-methoxy-2-phenylacetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[N-(furan-2-ylcarbonyl)glycyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(benzyloxy)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(naphthalen-1-ylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(N-benzoylglycyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{1-[4-(thiophen-2-yl)butanoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(2,5-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclobutylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-{N-[(4-methylphenyl)sulfonyl]glycyl}piperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2,3-difluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2S)-2-methoxy-2-phenylacetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(naphthalen-2-ylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-phenylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2,6-dichlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[3-(phenylsulfonyl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(2,5-dimethylfuran-3-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(1,3-thiazol-4-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(1,3-thiazol-5-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(ethoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(6-methylpyridin-3-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(furan-2-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(1-methylcyclohexyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-oxopropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopentylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-propanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(1,3-thiazol-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(tetrahydro-2H-pyran-4-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-{[4-(trifluoromethoxy)phenyl]acetyl}pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(thiophen-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(4-fluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(3,5-difluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(3-fluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({(3R)-1-[3-(trifluoromethyl)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(2,4-difluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-{[4-(trifluoromethyl)phenyl]acetyl}pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(1,3-thiazol-4-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(tetrahydrofuran-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(5-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(2-fluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({(3R)-1-[3-(trifluoromethoxy)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(pyridin-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(4-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-methyl-2-phenylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(methoxyacetyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(thiophen-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-{[3-(trifluoromethyl)phenyl]acetyl}pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2,2-dimethylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({(3R)-1-[4-(trifluoromethyl)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({(3R)-1-[4-(trifluoromethoxy)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3-methylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[difluoro(phenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(4,4-difluorocyclohexyl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(1,3-thiazol-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(tetrahydro-2H-pyran-4-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-{[4-(trifluoromethoxy)phenyl]acetyl}pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(4-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(thiophen-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(4-fluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide;     N-[4-({(3R)-1-[(3,5-difluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(3-fluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({(3R)-1-[3-(trifluoromethyl)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(2,4-difluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-{[4-(trifluoromethyl)phenyl]acetyl}pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(1,3-thiazol-4-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(tetrahydrofuran-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(5-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(2-fluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({(3R)-1-[3-(trifluoromethoxy)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(pyridin-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(4-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-methyl-2-phenylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(methoxyacetyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(thiophen-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-{[3-(trifluoromethyl)phenyl]acetyl}pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2,2-dimethylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({(3R)-1-[4-(trifluoromethyl)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({(3R)-1-[4-(trifluoromethoxy)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3-methylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[difluoro(phenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(4,4-difluorocyclohexyl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(4-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{1-[(3,5-difluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,4-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{1-[(3-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{1-[3-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-(4-{1-[(2,4-difluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(1,3-thiazol-4-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(pyridin-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(3-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methyl-2-phenylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-(1-{[3-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)phenyl]azetidine-3-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{1-[4-(trifluoromethoxy)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[difluoro(phenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{1-[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-(1-{[4-(trifluoromethoxy)phenyl]acetyl}piperidin-4-yl)phenyl]azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{1-[3-(trifluoromethoxy)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-(1-{[4-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)phenyl]azetidine-3-carboxamide; -   N-(4-{[1-(3-chlorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-tert-butylbenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-methoxybenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-methylbenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclohexylcarbonyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methoxybenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2S)-2-phenylbutanoyl]piperidin-4-yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[4-(propan-2-yl)benzoyl]piperidin-4-yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-chlorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-benzoylpiperidin-4-yl)sulfonyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]sulfonyl}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(2,5-difluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylbenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(4-fluorophenyl)acetyl]piperidin-4-yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylbenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,3-dimethylbenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(3-fluorophenyl)acetyl]piperidin-4-yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-fluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({1[3-(trifluoromethyl)benzoyl]piperidin-4-yl}sulfonyl)phenyl]azetidine-3-carboxamide; -   N-[4-({1-[(3,5-difluorophenyl)acetyl]piperidin-4-yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,4-difluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}sulfonyl)phenyl]azetidine-3-carboxamide; -   N-(4-{[1-(4-fluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,3-difluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,4-dichlorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(naphthalen-1-ylcarbonyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylcarbonyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3,5-difluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3,3-dimethylbutanoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methoxybenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylbutanoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylcarbonyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(phenylacetyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1-phenylcyclopropyl)carbonyl]piperidin-4-yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylalanyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3R)-1-(pyridin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3R)-1-(pyridazin-4-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3R)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3S)-1-(pyridazin-4-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3S)-1-(pyridin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   tert-butyl     4-(2-methyl-1-oxo-1-{4-[4-({[1-(pyridin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]piperidin-1-yl}propan-2-yl)piperazine-1-carboxylate; -   N-(4-{1[2-methyl-2-(piperazin-1-yl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-chlorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-methylpentanoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide;     N-[4-({1-[(2-fluorophenyl)acetyl]piperidin-4-yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[(1-benzoylpiperidin-4-yl)sulfonyl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-fluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylcarbonyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[(3R)-1-(5,6-dichloropyridazin-4-yl)pyrrolidin-3-yl]-5[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide; -   N-[(3R)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide; -   N-[(3S)-1-(5,6-dichloropyridazin-4-yl)pyrrolidin-3-yl]-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide; -   N-[(3S)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]-5[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide; -   N-[(3R)-1-(5,6-dichloropyridazin-4-yl)pyrrolidin-3-yl]-5[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-3-carboxamide; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3R)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-3-carboxamide; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3R)-1-(pyridazin-4-yl)pyrrolidin-3-yl]thiophene-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)piperidine-4-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)piperidine-4-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)piperidine-4-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}piperidine-4-carboxamide; -   N-[(3S)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(1,3-thiazol-5-ylcarbonyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2S)-2-phenylbutanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2S)-2-methoxy-2-phenylacetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2R)-2-methoxy-2-phenylacetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(ethoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(4-methylphenoxy)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(naphthalen-1-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2,6-dichlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(naphthalen-1-ylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-(4-{1-[4-(thiophen-2-yl)butanoyl]piperidin-4-yl}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,5-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(naphthalen-2-ylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[3-(phenylsulfonyl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-[4-(1-{[3-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)phenyl]pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(furan-2-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(N-benzoylglycyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2,4-dichlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(1-methylcyclohexyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(6-methylpyridin-3-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(3-chlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-propanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclopentylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclopropylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-fluoro-5-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(5-fluoropyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(2-fluoro-6-methylpyridin-3-yl)azetidine-3-carboxamide; -   (3S)—N-{4-[1-(2-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,4-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-heptanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,4-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(4-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,3-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-hexanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-butanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(3,5-dimethylphenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3,5-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-fluoro-2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(4-chlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(furan-3-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3,4-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[2-chloro-5-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-acetylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3,5-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-ethoxypropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,5-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,5-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(5-fluoro-2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(diphenylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-(4-{1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(pent-4-enoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-(4-{1-[3-(trifluoromethoxy)benzoyl]piperidin-4-yl}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(1-phenylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[2-fluoro-5-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclohexylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-methoxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-ethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-tert-butylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-(4-{1-[3-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(pent-4-ynoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(3-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[3-(methylsulfanyl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(1-acetylpiperidin-4-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(but-3-enoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-fluoro-4-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-methoxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2-chlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(N-acetyl-L-leucyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-cyanobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-methoxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,3-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[4-(propan-2-yl)benzoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclohexylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-hydroxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-cyanobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(2-cyanopyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(4-cyanopyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-fluoro-4-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(5-cyanopyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(5-methylpyridin-3-yl)azetidine-3-carboxamide; -   2-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]-1,3-thiazole-5-carboxamide; -   (3S)—N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(2-methylpyridin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(2-methylpyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   N-[(3S)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]furan-2-carboxamide; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]furan-2-carboxamide; -   N-(4-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[(3S)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]-4-[1-(2-methylpropanoyl)piperidin-4-yl]benzamide; -   N-(4-{1-[2-(piperazin-1-yl)ethyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   4-[1-(2-methylpropanoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]benzamide; -   N-{4-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   5-[1-(3-fluorobenzoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-[1-(4-fluorobenzoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   (3S)—N-(4-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]-5[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]thiophene-2-carboxamide; -   (3S)—N-{4-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   5-[1-(2-methylpropanoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-{1[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-(1-benzoylpiperidin-4-yl)-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]-5[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]thiophene-2-carboxamide; -   N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]-5-{1[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}thiophene-2-carboxamide; -   5-{1-[(1-methylpiperidin-4-yl)acetyl]piperidin-4-yl}-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]-5-[1-(1,3-thiazol-4-ylcarbonyl)piperidin-4-yl]thiophene-2-carboxamide; -   (3S)—N-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(propan-2-yl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclopropylmethyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-2-ylmethyl)-1H-pyrazol-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-tert-butyl-1H-pyrazol-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-benzoylpyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-(2-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-(3-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-(4-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-(2-methylbenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-({(3R)-1-[(4,4-difluorocyclohexyl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(4,4,4-trifluorobutanoyl)pyrrolidin-3-yl]oxy}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-[4-(5-propyl-1,2,4-oxadiazol-3-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   (3S)—N-{4-[1-(2-fluorobenzoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-fluorobenzoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-fluorobenzoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-benzoylazetidin-3-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,2-dimethylpropanoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3,5-difluorobenzoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-methylbenzoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,4-difluorobenzoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3R)—N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3R)—N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3R)—N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(cyclohexylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(3-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[(1-benzoylpiperidin-4-yl)oxy]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(4-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-({1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-{4-[5-(2,2-dimethylpropyl)-1,3,4-oxadiazol-2-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropyl)-1H-imidazol-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[5-(2,2-dimethylpropyl)-1,2,4-oxadiazol-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[3-cyclopropyl-1-(2-methoxyethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   tert-butyl     4-(5-{[1-(pyridazin-3-yl)azetidin-3-yl]carbamoyl}thiophen-2-yl)piperidine-1-carboxylate; -   tert-butyl     4-fluoro-4-[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]piperidine-1-carboxylate; -   5-(1-benzoylpiperidin-4-yl)-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2-methylbenzoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   5-[1-(3-fluorobenzoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   5-[1-(4-fluorobenzoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   5-[1-(3,5-difluorobenzoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   N-{4-[3-cyclopropyl-1-(2-hydroxyethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   1-(6-fluoropyridazin-3-yl)-N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(2-ethylbutanoyl)piperidin-4-yl]phenyl}-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   (3S)—N-(4-{[(3S)-1-benzoylpyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3S)-1-(2-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3S)-1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3S)-1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-{2-fluoro-4[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)-2-fluorophenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   (3S)—N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[(1-benzoylpiperidin-4-yl)oxy]phenyl}-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(cyclohexylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-{4[8-(2-methylpropanoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4[8-(4,4,4-trifluorobutanoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}azetidine-3-carboxamide; -   N-[4-(8-benzoyl-8-azabicyclo[3.2.1]oct-3-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[8-(2-fluorobenzoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4[8-(2,2-dimethylpropanoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{8-[(1-methylcyclopropyl)carbonyl]-8-azabicyclo[3.2.1]oct-3-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methoxyethyl)-3-(2-methylpropyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   5-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   5-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   N-[1-(pyridazin-3-yl)azetidin-3-yl]-5-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]thiophene-2-carboxamide; -   5-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   benzyl     4-[4-({[1-(6-chloropyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-4-fluoropiperidine-1-carboxylate; -   benzyl     4-[4-({[1-(6-chloropyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-4-hydroxypiperidine-1-carboxylate; -   N-[1-(pyridazin-3-yl)azetidin-3-yl]-5-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]thiophene-2-carboxamide; -   5-[1-(cyclopropylcarbonyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   N-{4-[4-fluoro-1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylcarbonyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(2-fluoro-4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoyl-4-fluoropiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)-4-fluoropiperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4[3-tert-butyl-1-(2-methoxyethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-butyl-3-tert-butyl-1H-pyrazol-5-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[3-tert-butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)-2-fluorophenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{1-[(4-methylpiperidin-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(6-chloropyridazin-3-yl)-N-{4-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]phenyl}azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(4-methylpiperidin-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-{3-fluoro-4[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{3-fluoro-4[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{3-fluoro-4[1-(3,3,3-tri     fluoropropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-3-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{3-fluoro-4[1-(4,4,4-tri     fluorobutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)-3-fluorophenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{3-fluoro-4[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-3-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{3-fluoro-4[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]-3-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)-4-hydroxypiperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)-4-hydroxypiperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(6-methylpyridazin-3-yl)-N-(4-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)azetidine-3-carboxamide; -   (3S)—N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-{4-[(1-benzoylpiperidin-4-yl)methyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3,3-dimethylbutanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-ethylbutanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-acetylpiperidin-4-yl)methyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-{[4-methyl-1-(oxetan-3-yl)piperidin-4-yl]methyl}-1H-pyrazol-4-yl)phenyl]-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(4-methylpyridazin-3-yl)azetidine-3-carboxamide; -   5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]furan-2-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(3-methylpyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(3-methylpyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2-aminopyridin-3-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-methyl-5-[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-1H-pyrazole-3-carboxylic     acid; -   ethyl     1-methyl-5-[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-1H-pyrazole-3-carboxylate; -   ethyl     1-phenyl-5-[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-1H-pyrazole-3-carboxylate; -   N-{6[1-(2-fluorobenzoyl)piperidin-4-yl]pyridin-3-yl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3-methylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   1-(6-methylpyridazin-3-yl)-N-(4-{[(3R)-1-(1,3-thiazol-4-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{6[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]pyridin-3-yl}azetidine-3-carboxamide; -   N-{6-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]pyridin-3-yl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   (3S)—N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(4-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(4-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-{4-[1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{6-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]pyridin-3-yl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   tert-butyl     4-[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)-1H-pyrazol-1-yl]piperidine-1-carboxylate; -   N-(6-{1-[(4-methylpiperidin-4-yl)methyl]-1H-pyrazol-4-yl}pyridin-yl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(1,3-thiazol-5-ylcarbonyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(1H-pyrazol-4-ylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylbutanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(methylsulfanyl)acetyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpentanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-methylpentanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[3-(methylsulfanyl)propanoyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(1,3-thiazol-4-ylcarbonyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(1H-pyrazol-5-ylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(6-methylpyridin-3-yl)carbonyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(pent-4-ynoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(methoxyacetyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(ethoxyacetyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-{4-[(1-hexanoylpiperidin-4-yl)methyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(but-3-enoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(furan-2-ylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(1,2-oxazol-5-ylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(pyridin-2-ylcarbonyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(furan-3-ylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylbutanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-propanoylpiperidin-4-yl)methyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-butanoylpiperidin-4-yl)methyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclobutylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-pentanoylpiperidin-4-yl)methyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylacetyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylbenzoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylpentanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclohexylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylbutanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(4-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-{1-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-1H-pyrazol-4-yl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{1-[1-(2-fluorobenzoyl)piperidin-4-yl]-1H-pyrazol-4-yl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(phenylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4[(2,2-dimethylpropyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(3-methoxy-2,2-dimethylpropyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4[(2-cyclopropylethyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[2-(2-ethylpiperidin-1-yl)ethyl]carbamoyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(cyclobutylmethyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(2S)-butan-2-ylcarbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(butylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(2,2-dimethyltetrahydro-2H-pyran-4-yl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(1S)-1-cyclopropylethyl]carbamoyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({2-[methyl(phenyl)amino]ethyl}carbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1,1′-bi(cyclopropyl)-1-ylcarbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-(thiophen-3-ylcarbamoyl)phenyl]azetidine-3-carboxamide; -   N-(4-{[(1R)-1-cyclopropylethyl]carbamoyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-methylpiperidin-4-yl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4[(2R)-butan-2-ylcarbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-azabicyclo[2.2.2]oct-3-ylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl}azetidine-3-carboxamide; -   N-{4-[(oxetan-3-ylmethyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(2-methylcyclopropyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(cyclobutylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-methylcyclopropyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(2-methoxy-2-methylpropyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(cyclopropylmethyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4[(3,3,3-trifluoropropyl)carbamoyl]phenyl}azetidine-3-carboxamide; -   N-{4[(1-methylpiperidin-3-yl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3-methyloxetan-3-yl)methyl]carbamoyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-(tetrahydro-2H-pyran-4-ylcarbamoyl)phenyl]azetidine-3-carboxamide; -   N-(4-{[(1-methylpiperidin-3-yl)methyl]carbamoyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(cyclopropylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(cyclopentylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(benzylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(3-fluorophenyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(propylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(4-fluorophenyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(2-fluorophenyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-methylcyclobutyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(prop-2-en-1-ylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   5-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]-5-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]thiophene-2-carboxamide; -   5-[1-(cyclopropylacetyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-[1-(bicyclo[2.2.1]hept-2-ylacetyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[(3S)-tetrahydrofuran-3-ylcarbamoyl]phenyl}azetidine-3-carboxamide; -   N-[4-({4-[2-(dimethylamino)ethyl]phenyl}carbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl}azetidine-3-carboxamide; -   N-{4-[(2-methoxy     ethyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-amino-2,2-dimethylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[2,2-dimethyl-3-(piperazin-1-yl)propyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1[2-methyl-2-(piperazin-1-yl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide;     and pharmaceutically acceptable salts thereof

Still another embodiment pertains to compounds of Formula (1A), selected from the group consisting of

-   N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   (3S)—N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-[4-(1-acetylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-butanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(methylsulfanyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-[4-(1-propanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   (3S)—N-[4-(1-propanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-butanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-acetylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-ethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3R)—N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide;     and pharmaceutically acceptable salts thereof.

Embodiments of Formula (IIC)

In another aspect, the present invention provides compounds of Formula (IIC)

and pharmaceutically acceptable salts thereof; wherein X¹, X², Y¹, R¹, and R² are as described herein for Formula (IC).

One embodiment of this invention pertains to compounds of Formula (IIC) and pharmaceutically acceptable salts thereof;

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is C(O)NH, or NHC(O);

R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I;

R² is independently selected from the group consisting of C₄-C₆-alkyl, C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl, and 5-6 membered heteroaryl; wherein each R² C₄-C₆-alkyl, C₄-C₆-alkenyl, and C₄-C₆-alkynyl is substituted with one or more substituents independently selected from the group consisting of R³, OR³, SR³, S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂, NHR³, N(R³)₂, NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³, NR³C(O)OR³, NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³, NR³C(O)N(R³)₂, C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³, C(O)NHSO₂R³, C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I;

R³, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and heterocyclyl; wherein each R³ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁵, OR⁵, SR⁵, S(O)R⁵, SO₂R⁵, C(O)R⁵, CO(O)R⁵, OC(O)R⁵, OC(O)OR⁵, NH₂, NHR⁵, N(R⁵)₂, NHC(O)R⁵, NR⁵C(O)R⁵, NHS(O)₂R⁵, NR⁵S(O)₂R⁵, NHC(O)OR⁵, NR⁵C(O)OR⁵, NHC(O)NH₂, NHC(O)NHR⁵, NHC(O)N(R⁵)₂, NR⁵C(O)NHR⁵, NR⁵C(O)N(R⁵)₂, C(O)NH₂, C(O)NHR⁵, C(O)N(R⁵)₂, C(O)NHOH, C(O)NHOR⁵, C(O)NHSO₂R⁵, C(O)NR⁵SO₂R⁵, SO₂NH₂, SO₂NHR⁵, SO₂N(R⁵)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁵, C(N)N(R⁵)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R³ aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁶, OR⁶, SR⁶, S(O)R⁶, SO₂R⁶, C(O)R⁶, CO(O)R⁶, OC(O)R⁶, OC(O)OR⁶, NH₂, NHR⁶, N(R⁶)₂, NHC(O)R⁶, NR⁶C(O)R⁶, NHS(O)₂R⁶, NR⁶S(O)₂R⁶, NHC(O)OR⁶, NR⁶C(O)OR⁶, NHC(O)NH₂, NHC(O)NHR⁶, NHC(O)N(R⁶)₂, NR⁶C(O)NHR⁶, NR⁶C(O)N(R⁶)₂, C(O)NH₂, C(O)NHR⁶, C(O)N(R⁶)₂, C(O)NHOH, C(O)NHOR⁶, C(O)NHSO₂R⁶, C(O)NR⁶SO₂R⁶, SO₂NH₂, SO₂NHR⁶, SO₂N(R⁶)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁶, C(N)N(R⁶)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I;

R⁵, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁵ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁸, OR⁸, SR⁸, S(O)R⁸, SO₂R⁸, NHR⁸, N(R⁸)₂, C(O)R⁸, C(O)NH₂, C(O)NHR⁸, C(O)N(R⁸)₂, NHC(O)R⁸, NR⁸C(O)R⁸, NHSO₂R⁸, NHC(O)OR⁸, SO₂NH₂, SO₂NHR⁸, SO₂N(R⁸)₂, NHC(O)NH₂, NHC(O)NHR⁸, OH, (O), C(O)OH, N₃, CN, NH₂, F, Cl, Br and I;

R⁶, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁶ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁹, OR⁹, SR⁹, S(O)R⁹, SO₂R⁹, NHR⁹, N(R⁹)₂, C(O)R⁹, C(O)NH₂, C(O)NHR⁹, C(O)N(R⁹)₂, NHC(O)R⁹, NR⁹C(O)R⁹, NHSO₂R⁹, NHC(O)OR⁹, SO₂NH₂, SO₂NHR⁹, SO₂N(R⁹)₂, NHC(O)NH₂, NHC(O)NHR⁹, OH, (O), C(O)OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br and I;

R⁷, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

R⁸, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

R⁹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein the cyclic moieties represented by R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹ are independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, C(O)C(O)R¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁶SO₂R¹⁶, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, CF₃, OCF₃, F, Cl, Br and I;

R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, OR¹³, C(O)OR¹³, OCF₃, CF₃, F, Cl, Br and I;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; and

R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl.

In one embodiment of Formula (IIC), X¹ is N and X² is CR¹; or X¹ is CR¹ and X² is N; or X¹ is CR¹ and X² is CR¹. In another embodiment of Formula (IIC), X¹ is N and X² is CR¹. In another embodiment of Formula (IIC), X¹ is CR¹ and X² is N. In another embodiment of Formula (IIC), X¹ is CR¹ and X² is CR¹.

In one embodiment of Formula (IIC), Y¹ is C(O)NH, or NHC(O). In another embodiment of Formula (IIC), Y¹ is C(O)NH. In another embodiment of Formula (IIC), Y¹ is NHC(O).

In one embodiment of Formula (IIC), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I. In another embodiment of Formula (IIC), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, Cl, Br and I. In another embodiment of Formula (IIC), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, and Cl. In another embodiment of Formula (IIC), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is hydrogen.

In another aspect, the present invention provides compounds of Formula (IID),

and pharmaceutically acceptable salts thereof; wherein R¹ and R² are as described herein for Formula (IC).

In one embodiment of Formula (IIC) and (IID), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I. In another embodiment of Formula (IIC) and (IID), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, Cl, Br and I. In another embodiment of Formula (IIC) and (IID), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, and Cl. In another embodiment of Formula (IIC) and (IID), R¹, at each occurrence, is hydrogen.

In one embodiment of Formula (IIC) and (IID), R² is independently selected from the group consisting of C₄-C₆-alkyl, C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl, and 5-6 membered heteroaryl; wherein each R² C₄-C₆-alkyl, C₄-C₆-alkenyl, and C₄-C₆-alkynyl is substituted with one or more substituents independently selected from the group consisting of R³, OR³, SR³, S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂, NHR³, N(R³)₂, NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³, NR³C(O)OR³, NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³, NR³C(O)N(R³)₂, C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³, C(O)NHSO₂R³, C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I. In another embodiment of Formula (IIC) and (IID), R² is aryl; wherein each R² aryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, C(O)NHR⁴, F, Cl, and I. In another embodiment of Formula (IIC) and (IID), R² is aryl; wherein each R² aryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, C(O)NHR⁴, and F. In another embodiment of Formula (IIC) and (IID), R² is phenyl; wherein each R² phenyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, C(O)NHR⁴, and F. In another embodiment of Formula (IIC) and (IID), R² is phenyl; wherein each R² phenyl is substituted with one substituent independently selected from the group consisting of R⁴, OR⁴, and SO₂R⁴.

In another embodiment of Formula (IIC) and (IID), R² is 5-6 membered heteroaryl; wherein each R² 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, C(O)NHR⁴, F, Cl, and I. In another embodiment of Formula (IIC) and (IID), R² is 5-6 membered heteroaryl; wherein each R² 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, C(O)NHR⁴, and F. In another embodiment of Formula (IIC) and (IID), R² is pyridinyl, furanyl, thiophenyl, pyrazole, or thiazolyl; wherein each R² pyridinyl, furanyl, thiophenyl, pyrazole, and thiazolyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, C(O)NHR⁴, and F.

In one embodiment of Formula (IIC) and (IID), R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I. In another embodiment of Formula (IIC) and (IID), R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl.

In one embodiment of Formula (IIC) and (IID), each R⁴ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I. In another embodiment of Formula (IIC) and (IID), each R⁴ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, N(R⁷)₂, F, Cl, Br and I.

In one embodiment of Formula (IIC) and (IID), R⁷, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl. In another embodiment of Formula (IIC) and (IID), R⁷, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl.

In one embodiment of Formula (IIC) and (IID), each R⁴ and R⁷ cyclic moiety is independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, CON(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, OR¹³, C(O)OR¹³, OCF₃, CF₃, F, Cl, Br and I; R¹², at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; and R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl.

In another embodiment of Formula (IIC) and (IID), each R⁴ and R⁷ cyclic moiety is independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, C(O)C(O)R¹⁰, CO(O)H, OH, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl, are optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, SO₂R¹¹, NH₂, N(R¹¹)₂, NHC(O)R¹¹, NHS(O)₂R¹¹, OH, NO₂, and F; wherein each R¹⁰ aryl, heterocyclyl and cycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², C(O)R¹², NH₂, OH, CN, CF₃, OCF₃, F, and Cl; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹¹ alkyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, CF₃, F, and Cl; R¹², at each occurrence, is independently selected from the group consisting of alkyl and aryl; and R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, and cycloalkyl.

One embodiment of this invention pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (IIC)

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is C(O)NH, or NHC(O);

R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, Cl, and F;

R² is aryl or 5-6 membered heteroaryl wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, SO₂R⁴, OR⁴, C(O)NHR⁴, and F; R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, and cycloalkyl; wherein each R⁴ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, N(R⁷)₂, and F;

R⁷, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl;

wherein the cyclic moieties represented by R⁴ and R⁷ are independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, C(O)R¹⁰, C(O)C(O)R¹⁰, CO(O)R¹⁰, C(O)OH, OH and F;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, SO₂R¹¹, NH₂, N(R¹¹)₂, NHC(O)R¹¹, NHS(O)₂R¹¹, OH, NO₂, and F; wherein each R¹⁰ aryl, heterocyclyl and cycloalkyl is optionally substituted with one or more R¹², OR¹², C(O)R¹², NH₂, OH, CN, CF₃, OCF₃, F, and Cl;

R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹¹ alkyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, C(O)OR¹³, OCF₃, CF₃, F, and Cl;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, and aryl; and

R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, cycloalkyl, and heterocyclyl.

Still another embodiment pertains to compounds having Formula (TIC), which includes

-   1-(pyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(2-cyanopyridin-3-yl)-N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)-1-[2-(trifluoromethyl)pyridin-3-yl]azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(4-methylpyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(4-fluoropyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)-1-[4-(trifluoromethyl)pyridin-3-yl]azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[1-(pyridin-3-yl)azetidin-3-yl]-4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}benzamide; -   N-(4-{1-[(2S)-2-methylbutanoyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)-N-[1-(pyridin-3-yl)azetidin-3-yl]benzamide; -   4-{[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]oxy}-N-[1-(pyridin-3-yl)azetidin-3-yl]benzamide; -   1-(pyridin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-[4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-{4-[(1-pentanoylpiperidin-4-yl)oxy]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-methylpentanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylpentanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-ethoxypropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3,3-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-butanoylpiperidin-4-yl)oxy]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(ethoxyacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(N-acetyl-L-leucyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclohexylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclohexylacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-(4-{[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1-methylcyclohexyl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(furan-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-{4-[(1-acetylpiperidin-4-yl)oxy]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(methoxyacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(morpholin-4-ylacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(furan-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-propanoylpiperidin-4-yl)oxy]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(N,N-dimethyl-beta-alanyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-(4-{[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,3-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(4-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(2-methoxypyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylmethyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpentyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylbutyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-ethylbutyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylpropyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylbutyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-propylpiperidin-4-yl)oxy]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-cyclopropylethyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-(4-{[1-(tetrahydrofuran-3-ylmethyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylbutyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclohexylmethyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopentylmethyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylbutyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylpentyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-butylpiperidin-4-yl)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-ethylbutyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylbutyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylpropyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-propylpiperidin-4-yl)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(4-methoxypyridin-3-yl)azetidine-3-carboxamide; -   1-(4-cyanopyridin-3-yl)-N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-[4-(1-pentanoylpiperidin-4-yl)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(morpholin-4-ylacetyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(furan-3-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-{4-[1-(pyrrolidin-1-ylacetyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(5-oxo-D-prolyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(N,N-dimethyl-beta-alanyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-{4-[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(4-methylpiperazin-1-yl)acetyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(5-oxo-L-prolyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-ethoxypropanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(1-methylcyclohexyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-acetylpiperidin-4-yl)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclohexylacetyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(N-acetyl-L-leucyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-propanoylpiperidin-4-yl)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[3-(morpholin-4-yl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(furan-2-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[3-(piperidin-1-yl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(ethoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-butanoylpiperidin-4-yl)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclohexylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopentylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2S)-2-methylbutanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,5-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-(4-{1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(pyridazin-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-[4-(1-pentanoylpiperidin-4-yl)phenyl]azetidine-3-carboxamide; -   N-{4-[1-(3-methylpentanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]piperidin-4-yl}phenyl)-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(morpholin-4-ylacetyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(furan-3-ylcarbonyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(pyrrolidin-1-ylacetyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(5-oxo-D-prolyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(N,N-dimethyl-beta-alanyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-(4-{1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(4-methylpiperazin-1-yl)acetyl]piperidin-4-yl}phenyl)-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(5-oxo-L-prolyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(3-ethoxypropanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-methylpentanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(1-methylcyclohexyl)carbonyl]piperidin-4-yl}phenyl)-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-acetylpiperidin-4-yl)phenyl]-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclohexylacetyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(N-acetyl-L-leucyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-[4-(1-propanoylpiperidin-4-yl)phenyl]azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}phenyl)-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-(4-{1-[3-(morpholin-4-yl)propanoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-(4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(furan-2-ylcarbonyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-(4-{1-[3-(piperidin-1-yl)propanoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(ethoxyacetyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-butanoylpiperidin-4-yl)phenyl]-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclohexylcarbonyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-fluorobenzoyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,4-difluorobenzoyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({1-[difluoro(phenyl)acetyl]azetidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({1-[(4,4-difluoro     cyclohexyl)carbonyl]azetidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({1-[(4-fluorophenyl)acetyl]azetidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({1-[4-(trifluoromethyl)benzoyl]azetidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-{4-[(1-benzoylazetidin-3-yl)oxy]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-hydroxy-2-methylpropanoyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydrofuran-3-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(furan-3-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[(1-pentanoylazetidin-3-yl)oxy]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[difluoro(phenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methyl-2-phenylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(1,3-thiazol-4-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[(1-{[4-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)oxy]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({1-[3-(trifluoromethyl)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({1[3-(trifluoromethoxy)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-(4-{[1-(3-methylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(3-fluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,4-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(4-fluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3,4-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({1-[4-(trifluoromethoxy)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-[4-({1-[(2,4-difluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[(1-{[4-(trifluoromethoxy)phenyl]acetyl}piperidin-4-yl)oxy]phenyl}azetidine-3-carboxamide; -   N-[4-({1-[(3,5-difluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[(1-{[3-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)oxy]phenyl}azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(pyridin-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(3,5-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-acetylpiperidin-4-yl)oxy]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(methoxyacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2-fluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(3-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3,3-dimethylbutanoyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclohexylcarbonyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(2-methylcyclopropyl)carbonyl]azetidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)azetidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylcarbonyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3,3-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclobutylcarbonyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydrofuran-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(4-methylpentanoyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropanoyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2S)-2-methylbutanoyl]azetidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(methoxyacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[difluoro(phenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({1-[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(1,3-thiazol-4-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[(1-{[4-(trifluoromethyl)phenyl]acetyl}     piperidin-4-yl)oxy]phenyl}azetidine-3-carboxamide; -   N-(4-{[1-(3,4-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[(1-{[4-(trifluoromethoxy)phenyl]acetyl}piperidin-4-yl)oxy]phenyl}azetidine-3-carboxamide; -   N-[4-({1-[(4-fluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2,4-difluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(2-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methyl-2-phenylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[(1-acetylpiperidin-4-yl)oxy]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(2,4-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({1-[3-(trifluoromethyl)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-(4-{[1-(3-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-[4-({1-[(3-fluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({1-[4-(trifluoromethoxy)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-[4-({1-[(3,5-difluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({1-[3-(trifluoromethoxy)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(pyridin-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(4-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(3,5-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[(1-{[3-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)oxy]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2-fluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]furan-2-carboxamide; -   tert-butyl     4-(4-{[1-(pyridazin-3-yl)azetidin-3-yl]carbamoyl}phenyl)piperidine-1-carboxylate; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   N-[4-(1-acetylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-butanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-pentanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-hexanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-ethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-heptanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(but-3-enoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(p     ent-4-enoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(methylsulfanyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-nitropropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[3-(methylsulfanyl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(pent-4-ynoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclohexylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclohexylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-hydroxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-hydroxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-hydroxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methoxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methoxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-methoxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-cyanobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-cyanobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{1-[3-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{1-[3-(trifluoromethoxy)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(2,3-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,4-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,5-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,4-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,5-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,4-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,5-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,4-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,5-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(3-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(4-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2-chlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(4-chlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-(1-{[4-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)phenyl]azetidine-3-carboxamide; -   N-(4-{1-[(3,5-dimethylphenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2,5-difluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(3,4-dichlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(furan-3-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(5-methylpyrazin-2-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-ethoxypropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(1-phenylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{1-[(pyrimidin-2-ylsulfanyl)acetyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-(4-{1-[(1-acetylpiperidin-4-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(3,5-difluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(N-acetyl-L-leucyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(diphenylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-fluoro-2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(5-fluoro-2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-fluoro-4-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,3-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[4-(propan-2-yl)benzoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-tert-butylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[2-fluoro-5-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[2-chloro-5-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(4-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(4-methylphenoxy)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2S)-2-phenylbutanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-(1-{[3-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)phenyl]azetidine-3-carboxamide; -   N-(4-{1-[(3-chlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2,4-dichlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(naphthalen-1-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2R)-2-methoxy-2-phenylacetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[N-(furan-2-ylcarbonyl)glycyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(benzyloxy)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(naphthalen-1-ylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(N-benzoylglycyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{1-[4-(thiophen-2-yl)butanoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(2,5-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclobutylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-{N-[(4-methylphenyl)sulfonyl]glycyl}piperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2,3-difluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2S)-2-methoxy-2-phenylacetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(naphthalen-2-ylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-phenylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2,6-dichlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[3-(phenylsulfonyl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(2,5-dimethylfuran-3-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(1,3-thiazol-4-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(1,3-thiazol-5-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(ethoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(6-methylpyridin-3-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(furan-2-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(1-methylcyclohexyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-oxopropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopentylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-propanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(1,3-thiazol-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(tetrahydro-2H-pyran-4-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-{[4-(trifluoromethoxy)phenyl]acetyl}pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(thiophen-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(4-fluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(3,5-difluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(3-fluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({(3R)-1-[3-(trifluoromethyl)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(2,4-difluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-{[4-(trifluoromethyl)phenyl]acetyl}pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(1,3-thiazol-4-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(tetrahydrofuran-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(5-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(2-fluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({(3R)-1-[3-(trifluoromethoxy)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(pyridin-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(4-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-methyl-2-phenylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(methoxyacetyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(thiophen-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-{[3-(trifluoromethyl)phenyl]acetyl}pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2,2-dimethylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({(3R)-1-[4-(trifluoromethyl)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({(3R)-1-[4-(trifluoromethoxy)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3-methylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[difluoro(phenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(4,4-difluorocyclohexyl)carbonyl]pyrrolidin-3-yl}     oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(1,3-thiazol-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(tetrahydro-2H-pyran-4-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-{[4-(trifluoromethoxy)phenyl]acetyl}pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(4-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(thiophen-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(4-fluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(3,5-difluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(3-fluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({(3R)-1-[3-(trifluoromethyl)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(2,4-difluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-{[4-(trifluoromethyl)phenyl]acetyl}pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(1,3-thiazol-4-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(tetrahydrofuran-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(5-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(2-fluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({(3R)-1-[3-(trifluoromethoxy)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(pyridin-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(4-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-methyl-2-phenylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(methoxyacetyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(thiophen-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-{[3-(trifluoromethyl)phenyl]acetyl}pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2,2-dimethylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({(3R)-1-[4-(trifluoromethyl)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({(3R)-1-[4-(trifluoromethoxy)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3-methylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[difluoro(phenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(4,4-difluorocyclohexyl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(4-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{1-[(3,5-difluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,4-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{1-[(3-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{1-[3-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-(4-{1-[(2,4-difluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(1,3-thiazol-4-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(pyridin-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(3-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methyl-2-phenylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-(1-{[3-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)phenyl]azetidine-3-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{1-[4-(trifluoromethoxy)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[difluoro(phenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{1-[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-(1-{[4-(trifluoromethoxy)phenyl]acetyl}piperidin-4-yl)phenyl]azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{1-[3-(trifluoromethoxy)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-(1-{[4-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)phenyl]azetidine-3-carboxamide; -   N-(4-{[1-(3-chlorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-tert-butylbenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-methoxybenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-methylbenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclohexylcarbonyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methoxybenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2S)-2-phenylbutanoyl]piperidin-4-yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[4-(propan-2-yl)benzoyl]piperidin-4-yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-chlorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-benzoylpiperidin-4-yl)sulfonyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]sulfonyl}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(2,5-difluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylbenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(4-fluorophenyl)acetyl]piperidin-4-yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylbenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,3-dimethylbenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(3-fluorophenyl)acetyl]piperidin-4-yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-fluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({1[3-(trifluoromethyl)benzoyl]piperidin-4-yl}sulfonyl)phenyl]azetidine-3-carboxamide; -   N-[4-({1-[(3,5-difluorophenyl)acetyl]piperidin-4-yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,4-difluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}sulfonyl)phenyl]azetidine-3-carboxamide; -   N-(4-{[1-(4-fluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,3-difluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,4-dichlorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(naphthalen-1-ylcarbonyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylcarbonyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3,5-difluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3,3-dimethylbutanoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methoxybenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylbutanoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylcarbonyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(phenylacetyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1-phenylcyclopropyl)carbonyl]piperidin-4-yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylalanyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   tert-butyl     4-(2-methyl-1-oxo-1-{4-[4-({[1-(pyridin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]piperidin-1-yl}propan-2-yl)piperazine-1-carboxylate; -   N-(4-{1[2-methyl-2-(piperazin-1-yl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-chlorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-methylpentanoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2-fluorophenyl)acetyl]piperidin-4-yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[(1-benzoylpiperidin-4-yl)sulfonyl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-fluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylcarbonyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-fluoro-5-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(5-fluoropyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(2-fluoro-6-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(2-cyanopyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(4-cyanopyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-fluoro-4-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(5-cyanopyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(5-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[2-(piperazin-1-yl)ethyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(5-propyl-1,2,4-oxadiazol-3-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[5-(2,2-dimethylpropyl)-1,3,4-oxadiazol-2-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropyl)-1H-imidazol-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[5-(2,2-dimethylpropyl)-1,2,4-oxadiazol-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[3-cyclopropyl-1-(2-methoxyethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   tert-butyl     4-fluoro-4-[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]piperidine-1-carboxylate; -   N-{4-[3-cyclopropyl-1-(2-hydroxyethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   1-(6-fluoropyridazin-3-yl)-N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(2-ethylbutanoyl)piperidin-4-yl]phenyl}-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)-2-fluorophenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4[8-(2-methylpropanoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4[8-(4,4,4-trifluorobutanoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}azetidine-3-carboxamide; -   N-[4-(8-benzoyl-8-azabicyclo[3.2.1]oct-3-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[8-(2-fluorobenzoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4[8-(2,2-dimethylpropanoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{8-[(1-methylcyclopropyl)carbonyl]-8-azabicyclo[3.2.1]oct-3-yl}     phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methoxyethyl)-3-(2-methylpropyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   benzyl     4-[4-({[1-(6-chloropyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-4-fluoropiperidine-1-carboxylate; -   benzyl     4-[4-({[1-(6-chloropyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-4-hydroxypiperidine-1-carboxylate; -   N-{4-[4-fluoro-1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylcarbonyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(2-fluoro-4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoyl-4-fluoropiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)-4-fluoropiperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4[3-tert-butyl-1-(2-methoxyethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-butyl-3-tert-butyl-1H-pyrazol-5-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4[3-tert-butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)-2-fluorophenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{1-[(4-methylpiperidin-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(6-chloropyridazin-3-yl)-N-{4-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]phenyl}azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(4-methylpiperidin-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-{3-fluoro-4[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{3-fluoro-4[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{3-fluoro-4[1-(3,3,3-tri     fluoropropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-3-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{3-fluoro-4[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)-3-fluorophenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{3-fluoro-4[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-3-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{3-fluoro-4[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]-3-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)-4-hydroxypiperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)-4-hydroxypiperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(6-methylpyridazin-3-yl)-N-(4-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[(1-benzoylpiperidin-4-yl)methyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3,3-dimethylbutanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-ethylbutanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-acetylpiperidin-4-yl)methyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-{[4-methyl-1-(oxetan-3-yl)piperidin-4-yl]methyl}-1H-pyrazol-4-yl)phenyl]-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(4-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(3-methylpyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(3-methylpyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2-aminopyridin-3-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-methyl-5-[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-1H-pyrazole-3-carboxylic     acid; -   ethyl     1-methyl-5-[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-1H-pyrazole-3-carboxylate; -   ethyl     1-phenyl-5-[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-1H-pyrazole-3-carboxylate; -   N-{6[1-(2-fluorobenzoyl)piperidin-4-yl]pyridin-3-yl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3-methylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   1-(6-methylpyridazin-3-yl)-N-(4-{[(3R)-1-(1,3-thiazol-4-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{6[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]pyridin-3-yl}azetidine-3-carboxamide; -   N-{6-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]pyridin-3-yl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{6-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]pyridin-3-yl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   tert-butyl     4-[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)-1H-pyrazol-1-yl]piperidine-1-carboxylate; -   N-(6-{1-[(4-methylpiperidin-4-yl)methyl]-1H-pyrazol-4-yl}pyridin-yl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(1,3-thiazol-5-ylcarbonyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(1H-pyrazol-4-ylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylbutanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-{1-[(methylsulfanyl)acetyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpentanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-methylpentanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[3-(methylsulfanyl)propanoyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(1,3-thiazol-4-ylcarbonyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(1H-pyrazol-5-ylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(6-methylpyridin-3-yl)carbonyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(pent-4-ynoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(methoxyacetyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(ethoxyacetyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-{4-[(1-hexanoylpiperidin-4-yl)methyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(but-3-enoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(furan-2-ylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(1,2-oxazol-5-ylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(pyridin-2-ylcarbonyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(furan-3-ylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylbutanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-propanoylpiperidin-4-yl)methyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-butanoylpiperidin-4-yl)methyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclobutylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-pentanoylpiperidin-4-yl)methyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylacetyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylbenzoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylpentanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclohexylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylbutanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(4-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-{1-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-1H-pyrazol-4-yl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{1-[1-(2-fluorobenzoyl)piperidin-4-yl]-1H-pyrazol-4-yl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(phenylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4[(2,2-dimethylpropyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(3-methoxy-2,2-dimethylpropyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4[(2-cyclopropylethyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[2-(2-ethylpiperidin-1-yl)ethyl]carbamoyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(cyclobutylmethyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(2S)-butan-2-ylcarbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(butylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(2,2-dimethyltetrahydro-2H-pyran-4-yl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(1S)-1-cyclopropylethyl]carbamoyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({2-[methyl(phenyl)amino]ethyl}carbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1,1′-bi(cyclopropyl)-1-ylcarbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-(thiophen-3-ylcarbamoyl)phenyl]azetidine-3-carboxamide; -   N-(4-{[(1R)-1-cyclopropylethyl]carbamoyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-methylpiperidin-4-yl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4[(2R)-butan-2-ylcarbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-azabicyclo[2.2.2]oct-3-ylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl}azetidine-3-carboxamide; -   N-{4-[(oxetan-3-ylmethyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(2-methylcyclopropyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(cyclobutylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-methylcyclopropyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(2-methoxy-2-methylpropyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(cyclopropylmethyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4[(3,3,3-trifluoropropyl)carbamoyl]phenyl}azetidine-3-carboxamide; -   N-{4[(1-methylpiperidin-3-yl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3-methyloxetan-3-yl)methyl]carbamoyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-(tetrahydro-2H-pyran-4-ylcarbamoyl)phenyl]azetidine-3-carboxamide; -   N-(4-{[(1-methylpiperidin-3-yl)methyl]carbamoyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(cyclopropylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(cyclopentylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(benzylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(3-fluorophenyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(propylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(4-fluorophenyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(2-fluorophenyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-methylcyclobutyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(prop-2-en-1-ylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[(3S)-tetrahydrofuran-3-ylcarbamoyl]phenyl}azetidine-3-carboxamide; -   N-[4-({4-[2-(dimethylamino)ethyl]phenyl}carbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl}azetidine-3-carboxamide; -   N-{4-[(2-methoxy     ethyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-amino-2,2-dimethylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[2,2-dimethyl-3-(piperazin-1-yl)propyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1[2-methyl-2-(piperazin-1-yl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide;     and pharmaceutically acceptable salts thereof

Embodiments of Formula (IIIC)

In another aspect, the present invention provides compounds of Formula (IIIC)

and pharmaceutically acceptable salts thereof; wherein X¹, X², R¹, and Y¹ are as described in Formula (IC) herein and R^(4x) is as described herein for substituents on R² when R² is aryl in Formula (IC).

One embodiment of this invention pertains to compounds of Formula (IIIC) or pharmaceutically acceptable salts thereof;

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is C(O)NH, or NHC(O);

R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I;

R^(4X) is independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I;

R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SW, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I;

R⁷, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

wherein the cyclic moieties represented by R⁴ and R⁷, are independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, C(O)C(O)R¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, CF₃, OCF₃, F, Cl, Br and I;

R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, OR¹³, C(O)OR¹³, OCF₃, CF₃, F, Cl, Br and I;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; and

R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl.

In one embodiment of Formula (IIIC), X¹ is N and X² is CR¹; or X¹ is CR¹ and X² is N; or X¹ is CR¹ and X² is CR¹. In another embodiment of Formula (IIIC), X¹ is N and X² is CR¹. In another embodiment of Formula (IIIC), X¹ is CR¹ and X² is N. In another embodiment of Formula (IIIC), X¹ is CR¹ and X² is CR¹.

In one embodiment of Formula (IIIC), Y¹ is C(O)NH, or NHC(O). In another embodiment of Formula (IIIC), Y¹ is C(O)NH. In another embodiment of Formula (IIIC), Y¹ is NHC(O).

In one embodiment of Formula (IIIC), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I. In another embodiment of Formula (IIIC), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, Cl, Br and I. In another embodiment of Formula (IIIC), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, and Cl. In another embodiment of Formula (IIIC), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is hydrogen.

In another aspect, the present invention provides compounds of Formula (IIID),

and pharmaceutically acceptable salts thereof; wherein R¹ is described herein for Formula (IC) and R^(4x) is as described herein for substituents on R² when R² is aryl in Formula (IC).

In one embodiment of Formula (IIIC) and (IIID), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I. In another embodiment of Formula (IIIC) and (IIID), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, Cl, Br and I. In another embodiment of Formula (IIIC) and (IIID), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, and Cl. In another embodiment of Formula (IIIC) and (IIID), R¹, at each occurrence, is hydrogen.

In one embodiment of Formula (IIIC) and (IIID), R^(4X) is independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I. In another embodiment of Formula (IIIC) and (IIID), R^(4X) is independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, C(O)NHR⁴, F, Cl, and I. In another embodiment of Formula (IIIC) and (IIID), R^(4X) is independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, C(O)NHR⁴, and F.

In one embodiment of Formula (IIIC) and (IIID), R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I. In another embodiment of Formula (IIIC) and (IIID), R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl.

In one embodiment of Formula (IIIC) and (IIID), each R⁴ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I. In another embodiment of Formula (IIIC) and (IIID), each R⁴ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, N(R⁷)₂, F, Cl, Br and I.

In one embodiment of Formula (IIIC) and (IIID), R⁷, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl. In another embodiment of Formula (IIIC) and (IIID), R⁷, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl.

In one embodiment of Formula (IIIC) and (IIID), each R⁴ and R⁷ cyclic moiety is independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, OR¹³, C(O)OR¹³, OCF₃, CF₃, F, Cl, Br and I; R¹², at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; and R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl.

In another embodiment of Formula (IIIC) and (IIID), each R⁴ and R⁷ cyclic moiety is independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, C(O)C(O)R¹⁰, CO(O)H, OH, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl, are optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, SO₂R¹¹, NH₂, N(R¹¹)₂, NHC(O)R¹¹, NHS(O)₂R¹¹, OH, NO₂, and F; wherein each R¹⁰ aryl, heterocyclyl and cycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², C(O)R¹², NH₂, OH, CN, CF₃, OCF₃, F, and Cl; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹¹ alkyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, CF₃, F, and Cl; R¹², at each occurrence, is independently selected from the group consisting of alkyl and aryl; and R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, and cycloalkyl.

One embodiment of this invention pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (IIIC)

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is C(O)NH, or NHC(O);

R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, Cl, and F;

R^(4X) is independently selected from the group consisting of R⁴, SO₂R⁴, OR⁴, and F;

R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, and cycloalkyl; wherein each R⁴ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, N(R⁷)₂, and F;

R⁷, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl;

wherein the cyclic moieties represented by R⁴ and R⁷ are independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, C(O)R¹⁰, C(O)C(O)R¹⁰, CO(O)R¹⁰, C(O)OH, OH and F;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, SO₂R¹¹, NH₂, N(R¹¹)₂, NHC(O)R¹¹, NHS(O)₂R¹¹, OH, NO₂, and F; wherein each R¹⁰ aryl, heterocyclyl and cycloalkyl is optionally substituted with one or more R¹², OR¹², C(O)R¹², NH₂, OH, CN, CF₃, OCF₃, F, and Cl;

R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹¹ alkyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, C(O)OR¹³, OCF₃, CF₃, F, and Cl;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, and aryl; and

R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, cycloalkyl, and heterocyclyl.

Still another embodiment pertains to compounds having Formula (IIIC), which include

-   1-(pyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(2-cyanopyridin-3-yl)-N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)-1-[2-(trifluoromethyl)pyridin-3-yl]azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(4-methylpyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(4-fluoropyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)-1-[4-(trifluoromethyl)pyridin-3-yl]azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2S)-2-methylbutanoyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-[4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-{4-[(1-pentanoylpiperidin-4-yl)oxy]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-methylpentanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylpentanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-ethoxypropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3,3-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-butanoylpiperidin-4-yl)oxy]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(ethoxyacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(N-acetyl-L-leucyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclohexylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclohexylacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-(4-{[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1-methylcyclohexyl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(furan-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-{4-[(1-acetylpiperidin-4-yl)oxy]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(methoxyacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(morpholin-4-ylacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(furan-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-propanoylpiperidin-4-yl)oxy]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(N,N-dimethyl-beta-alanyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-(4-{[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,3-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(4-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(2-methoxypyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylmethyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpentyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylbutyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-ethylbutyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylpropyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylbutyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-propylpiperidin-4-yl)oxy]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-cyclopropylethyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-(4-{[1-(tetrahydrofuran-3-ylmethyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylbutyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclohexylmethyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopentylmethyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylbutyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylpentyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-butylpiperidin-4-yl)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-ethylbutyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylbutyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylpropyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-propylpiperidin-4-yl)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(4-methoxypyridin-3-yl)azetidine-3-carboxamide; -   1-(4-cyanopyridin-3-yl)-N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-[4-(1-pentanoylpiperidin-4-yl)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(morpholin-4-ylacetyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(furan-3-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-{4-[1-(pyrrolidin-1-ylacetyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(5-oxo-D-prolyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(N,N-dimethyl-beta-alanyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-{4-[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(4-methylpiperazin-1-yl)acetyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(5-oxo-L-prolyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-ethoxypropanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(1-methylcyclohexyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-acetylpiperidin-4-yl)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclohexylacetyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(N-acetyl-L-leucyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-propanoylpiperidin-4-yl)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[3-(morpholin-4-yl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   1-(pyridin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(furan-2-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[3-(piperidin-1-yl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(ethoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-butanoylpiperidin-4-yl)phenyl]-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclohexylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopentylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2S)-2-methylbutanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,5-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-(4-{1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(pyridazin-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-[4-(1-pentanoylpiperidin-4-yl)phenyl]azetidine-3-carboxamide; -   N-{4-[1-(3-methylpentanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]piperidin-4-yl}phenyl)-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(morpholin-4-ylacetyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(furan-3-ylcarbonyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(pyrrolidin-1-ylacetyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(5-oxo-D-prolyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(N,N-dimethyl-beta-alanyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-(4-{1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(4-methylpiperazin-1-yl)acetyl]piperidin-4-yl}phenyl)-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(5-oxo-L-prolyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(3-ethoxypropanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-methylpentanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(1-methylcyclohexyl)carbonyl]piperidin-4-yl}phenyl)-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-acetylpiperidin-4-yl)phenyl]-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclohexylacetyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(N-acetyl-L-leucyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-[4-(1-propanoylpiperidin-4-yl)phenyl]azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}phenyl)-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-(4-{1-[3-(morpholin-4-yl)propanoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-(4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(furan-2-ylcarbonyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   1-(2-methylpyridin-3-yl)-N-(4-{1-[3-(piperidin-1-yl)propanoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(ethoxyacetyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-butanoylpiperidin-4-yl)phenyl]-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclohexylcarbonyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-fluorobenzoyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,4-difluorobenzoyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({1-[difluoro(phenyl)acetyl]azetidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({1-[(4,4-difluoro     cyclohexyl)carbonyl]azetidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({1-[(4-fluorophenyl)acetyl]azetidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({1-[4-(trifluoromethyl)benzoyl]azetidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-{4-[(1-benzoylazetidin-3-yl)oxy]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-hydroxy-2-methylpropanoyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydrofuran-3-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(furan-3-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[(1-pentanoylazetidin-3-yl)oxy]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide;     N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[difluoro(phenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methyl-2-phenylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(1,3-thiazol-4-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[(1-{[4-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)oxy]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({1[3-(trifluoromethyl)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({1-[3-(trifluoromethoxy)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-(4-{[1-(3-methylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(3-fluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,4-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(4-fluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3,4-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({1-[4-(trifluoromethoxy)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-[4-({1-[(2,4-difluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[(1-{[4-(trifluoromethoxy)phenyl]acetyl}piperidin-4-yl)oxy]phenyl}azetidine-3-carboxamide; -   N-[4-({1-[(3,5-difluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[(1-{[3-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)oxy]phenyl}azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(pyridin-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(3,5-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-acetylpiperidin-4-yl)oxy]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(methoxyacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2-fluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(3-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3,3-dimethylbutanoyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclohexylcarbonyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(2-methylcyclopropyl)carbonyl]azetidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)azetidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylcarbonyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3,3-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclobutylcarbonyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydrofuran-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(4-methylpentanoyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropanoyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2S)-2-methylbutanoyl]azetidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(methoxyacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[difluoro(phenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({1-[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(1,3-thiazol-4-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[(1-{[4-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)oxy]phenyl}azetidine-3-carboxamide; -   N-(4-{[1-(3,4-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[(1-{[4-(trifluoromethoxy)phenyl]acetyl}piperidin-4-yl)oxy]phenyl}azetidine-3-carboxamide; -   N-[4-({1-[(4-fluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2,4-difluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(2-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methyl-2-phenylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[(1-acetylpiperidin-4-yl)oxy]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(2,4-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({1-[3-(trifluoromethyl)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-(4-{[1-(3-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-[4-({1-[(3-fluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({1-[4-(trifluoromethoxy)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-[4-({1-[(3,5-difluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({1-[3-(trifluoromethoxy)benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(pyridin-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(4-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(3,5-difluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[(1-{[3-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)oxy]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2-fluorophenyl)acetyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-(1-acetylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-butanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-pentanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide;     N-[4-(1-hexanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-ethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-heptanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(but-3-enoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(p     ent-4-enoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(methylsulfanyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-nitropropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[3-(methylsulfanyl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(pent-4-ynoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclohexylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclohexylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-hydroxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-hydroxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-hydroxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methoxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-methoxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-methoxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-cyanobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-cyanobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{1-[3-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{1-[3-(trifluoromethoxy)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(2,3-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,4-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,5-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,4-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,5-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,4-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,5-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,4-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,5-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(3-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(4-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2-chlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(4-chlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-(1-{[4-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)phenyl]azetidine-3-carboxamide; -   N-(4-{1-[(3,5-dimethylphenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2,5-difluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(3,4-dichlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(furan-3-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(5-methylpyrazin-2-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-ethoxypropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(1-phenylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{1-[(pyrimidin-2-ylsulfanyl)acetyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-(4-{1-[(1-acetylpiperidin-4-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(3,5-difluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(N-acetyl-L-leucyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(diphenylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-fluoro-2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(5-fluoro-2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-fluoro-4-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,3-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[4-(propan-2-yl)benzoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-tert-butylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[2-fluoro-5-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[2-chloro-5-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(4-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(4-methylphenoxy)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2S)-2-phenylbutanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-(1-{[3-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)phenyl]azetidine-3-carboxamide; -   N-(4-{1-[(3-chlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2,4-dichlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(naphthalen-1-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2R)-2-methoxy-2-phenylacetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[N-(furan-2-ylcarbonyl)glycyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(benzyloxy)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(naphthalen-1-ylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(N-benzoylglycyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{1-[4-(thiophen-2-yl)butanoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(2,5-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclobutylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-{N-[(4-methylphenyl)sulfonyl]glycyl}piperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2,3-difluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2S)-2-methoxy-2-phenylacetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(naphthalen-2-ylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-phenylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2,6-dichlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[3-(phenylsulfonyl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(2,5-dimethylfuran-3-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(1,3-thiazol-4-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(1,3-thiazol-5-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(ethoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(6-methylpyridin-3-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(furan-2-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(1-methylcyclohexyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-oxopropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopentylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-propanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(1,3-thiazol-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(tetrahydro-2H-pyran-4-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-{[4-(trifluoromethoxy)phenyl]acetyl}pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(thiophen-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(4-fluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(3,5-difluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide;     N-[4-({(3R)-1-[(3-fluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({(3R)-1-[3-(trifluoromethyl)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(2,4-difluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-{[4-(trifluoromethyl)phenyl]acetyl}pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(1,3-thiazol-4-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(tetrahydrofuran-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(5-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(2-fluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({(3R)-1-[3-(trifluoromethoxy)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(pyridin-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(4-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-methyl-2-phenylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(methoxyacetyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(thiophen-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-{[3-(trifluoromethyl)phenyl]acetyl}pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2,2-dimethylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({(3R)-1-[4-(trifluoromethyl)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-({(3R)-1-[4-(trifluoromethoxy)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3-methylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[difluoro(phenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(4,4-difluorocyclohexyl)carbonyl]pyrrolidin-3-yl}     oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(1,3-thiazol-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(tetrahydro-2H-pyran-4-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-{[4-(trifluoromethoxy)phenyl]acetyl}pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(4-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(thiophen-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(4-fluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(3,5-difluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(3-fluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({(3R)-1-[3-(trifluoromethyl)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(2,4-difluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-{[4-(trifluoromethyl)phenyl]acetyl}pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(1,3-thiazol-4-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(tetrahydrofuran-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(5-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(2-fluorophenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({(3R)-1-[3-(trifluoromethoxy)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(pyridin-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(4-chlorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-methyl-2-phenylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(methoxyacetyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(thiophen-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-{[3-(trifluoromethyl)phenyl]acetyl}pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2,2-dimethylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({(3R)-1-[4-(trifluoromethyl)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({(3R)-1-[4-(trifluoromethoxy)benzoyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(3-methylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[difluoro(phenyl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({(3R)-1-[(4,4-difluorocyclohexyl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(4-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{1-[(3,5-difluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,4-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{1-[(3-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{1-[3-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-(4-{1-[(2,4-difluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(1,3-thiazol-4-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(pyridin-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(3-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methyl-2-phenylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-(1-{[3-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)phenyl]azetidine-3-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{1-[4-(trifluoromethoxy)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-(4-{1-[difluoro(phenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{1-[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-(1-{[4-(trifluoromethoxy)phenyl]acetyl}piperidin-4-yl)phenyl]azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-(4-{1-[3-(trifluoromethoxy)benzoyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-4-yl)-N-[4-(1-{[4-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)phenyl]azetidine-3-carboxamide; -   N-(4-{[1-(3-chlorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-tert-butylbenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-methoxybenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-methylbenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclohexylcarbonyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methoxybenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2S)-2-phenylbutanoyl]piperidin-4-yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[4-(propan-2-yl)benzoyl]piperidin-4-yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-chlorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-benzoylpiperidin-4-yl)sulfonyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]sulfonyl}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(2,5-difluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylbenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(4-fluorophenyl)acetyl]piperidin-4-yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylbenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,3-dimethylbenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(3-fluorophenyl)acetyl]piperidin-4-yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-fluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({1[3-(trifluoromethyl)benzoyl]piperidin-4-yl}sulfonyl)phenyl]azetidine-3-carboxamide; -   N-[4-({1-[(3,5-difluorophenyl)acetyl]piperidin-4-yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,4-difluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-({1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}sulfonyl)phenyl]azetidine-3-carboxamide; -   N-(4-{[1-(4-fluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,3-difluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,4-dichlorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(naphthalen-1-ylcarbonyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylcarbonyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3,5-difluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3,3-dimethylbutanoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methoxybenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylbutanoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylcarbonyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(phenylacetyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide;     N-[4-({1-[(1-phenylcyclopropyl)carbonyl]piperidin-4-yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methylalanyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide; -   tert-butyl     4-(2-methyl-1-oxo-1-{4-[4-({[1-(pyridin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]piperidin-1-yl}propan-2-yl)piperazine-1-carboxylate; -   N-(4-{1[2-methyl-2-(piperazin-1-yl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-chlorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-methylpentanoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2-fluorophenyl)acetyl]piperidin-4-yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[(1-benzoylpiperidin-4-yl)sulfonyl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-fluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylcarbonyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-fluoro-5-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(5-fluoropyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(2-fluoro-6-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(2-cyanopyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(4-cyanopyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-fluoro-4-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(5-cyanopyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(5-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[2-(piperazin-1-yl)ethyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(5-propyl-1,2,4-oxadiazol-3-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[5-(2,2-dimethylpropyl)-1,3,4-oxadiazol-2-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropyl)-1H-imidazol-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[5-(2,2-dimethylpropyl)-1,2,4-oxadiazol-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[3-cyclopropyl-1-(2-methoxyethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   tert-butyl     4-fluoro-4-[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]piperidine-1-carboxylate; -   N-{4-[3-cyclopropyl-1-(2-hydroxyethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   1-(6-fluoropyridazin-3-yl)-N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(2-ethylbutanoyl)piperidin-4-yl]phenyl}-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   N-{4[8-(2-methylpropanoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4[8-(4,4,4-trifluorobutanoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}azetidine-3-carboxamide; -   N-[4-(8-benzoyl-8-azabicyclo[3.2.1]oct-3-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[8-(2-fluorobenzoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4[8-(2,2-dimethylpropanoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{8-[(1-methylcyclopropyl)carbonyl]-8-azabicyclo[3.2.1]oct-3-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methoxyethyl)-3-(2-methylpropyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   benzyl     4-[4-({[1-(6-chloropyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-4-fluoropiperidine-1-carboxylate; -   benzyl     4-[4-({[1-(6-chloropyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-4-hydroxypiperidine-1-carboxylate; -   N-{4-[4-fluoro-1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoyl-4-fluoropiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)-4-fluoropiperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4[3-tert-butyl-1-(2-methoxyethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-butyl-3-tert-butyl-1H-pyrazol-5-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4[3-tert-butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(4-methylpiperidin-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(6-chloropyridazin-3-yl)-N-{4-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]phenyl}azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[(4-methylpiperidin-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)-4-hydroxypiperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)-4-hydroxypiperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(6-methylpyridazin-3-yl)-N-(4-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)azetidine-3-carboxamide; -   N-{4-[(1-benzoylpiperidin-4-yl)methyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3,3-dimethylbutanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-ethylbutanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4[(1-acetylpiperidin-4-yl)methyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-{[4-methyl-1-(oxetan-3-yl)piperidin-4-yl]methyl}-1H-pyrazol-4-yl)phenyl]-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(4-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(3-methylpyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(3-methylpyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{1-[(2-aminopyridin-3-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-methyl-5-[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-1H-pyrazole-3-carboxylic     acid; -   ethyl     1-methyl-5-[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-1H-pyrazole-3-carboxylate; -   ethyl     1-phenyl-5-[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-1H-pyrazole-3-carboxylate; -   N-(4-{[(3R)-1-(3-methylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3R)-1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   1-(6-methylpyridazin-3-yl)-N-(4-{[(3R)-1-(1,3-thiazol-4-yl     carbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide; -   N-{4-[1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(1,3-thiazol-5-ylcarbonyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(1H-pyrazol-4-ylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2,2-dimethylbutanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(methylsulfanyl)acetyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylpentanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-methylpentanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[3-(methylsulfanyl)propanoyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(1,3-thiazol-4-ylcarbonyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(1H-pyrazol-5-ylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(6-methylpyridin-3-yl)carbonyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(pent-4-ynoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(methoxyacetyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-[4-({1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(ethoxyacetyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-{4-[(1-hexanoylpiperidin-4-yl)methyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(but-3-enoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(furan-2-ylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(1,2-oxazol-5-ylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(pyridin-2-ylcarbonyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-(4-{[1-(furan-3-ylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylbutanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-propanoylpiperidin-4-yl)methyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-butanoylpiperidin-4-yl)methyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclobutylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-pentanoylpiperidin-4-yl)methyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylacetyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(2-methylbenzoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylpentanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclohexylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(3-methylbutanoyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopropylcarbonyl)piperidin-4-yl]methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(4-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(phenylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4[(2,2-dimethylpropyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(3-methoxy-2,2-dimethylpropyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4[(2-cyclopropylethyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[2-(2-ethylpiperidin-1-yl)ethyl]carbamoyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(cyclobutylmethyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(2S)-butan-2-ylcarbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(butylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(2,2-dimethyltetrahydro-2H-pyran-4-yl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(1S)-1-cyclopropylethyl]carbamoyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-({2-[methyl(phenyl)amino]ethyl}carbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1,1′-bi(cyclopropyl)-1-ylcarbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-(thiophen-3-ylcarbamoyl)phenyl]azetidine-3-carboxamide; -   N-(4-{[(1R)-1-cyclopropylethyl]carbamoyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-methylpiperidin-4-yl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4[(2R)-butan-2-ylcarbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-azabicyclo[2.2.2]oct-3-ylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl}azetidine-3-carboxamide; -   N-{4-[(oxetan-3-ylmethyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(2-methylcyclopropyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(cyclobutylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-methylcyclopropyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(2-methoxy-2-methylpropyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(cyclopropylmethyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4[(3,3,3-trifluoropropyl)carbamoyl]phenyl}azetidine-3-carboxamide; -   N-{4[(1-methylpiperidin-3-yl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{[(3-methyloxetan-3-yl)methyl]carbamoyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-(4-{[(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl}phenyl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl}azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-[4-(tetrahydro-2H-pyran-4-ylcarbamoyl)phenyl]azetidine-3-carboxamide; -   N-(4-{[(1-methylpiperidin-3-yl)methyl]carbamoyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(cyclopropylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(cyclopentylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(benzylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(3-fluorophenyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(propylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(4-fluorophenyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(2-fluorophenyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[(1-methylcyclobutyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(prop-2-en-1-ylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[(3S)-tetrahydrofuran-3-ylcarbamoyl]phenyl}azetidine-3-carboxamide; -   N-[4-({4-[2-(dimethylamino)ethyl]phenyl}carbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl}azetidine-3-carboxamide; -   N-{4-[(2-methoxy     ethyl)carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3-amino-2,2-dimethylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[2,2-dimethyl-3-(piperazin-1-yl)propyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{1-[2-methyl-2-(piperazin-1-yl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide;     and pharmaceutically acceptable salts thereof

Embodiments of Formula (IVC)

In another aspect, the present invention provides compounds of Formula (IVC)

and pharmaceutically acceptable salts thereof; wherein each X¹, X², Y¹, R¹, and R² are as described herein for Formula (I).

One embodiment of this invention pertains to compounds of Formula (IVC) and pharmaceutically acceptable salts thereof;

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is C(O)NH, or NHC(O);

R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I;

R² is independently selected from the group consisting of C₄-C₆-alkyl, C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl, and 5-6 membered heteroaryl; wherein each R² C₄-C₆-alkyl, C₄-C₆-alkenyl, and C₄-C₆-alkynyl is substituted with one or more substituents independently selected from the group consisting of R³, OR³, SR³, S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂, NHR³, N(R³)₂, NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³, NR³C(O)OR³, NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³, NR³C(O)N(R³)₂, C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³, C(O)NHSO₂R³, C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I;

R³, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and heterocyclyl; wherein each R³ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁵, OR⁵, SR⁵, S(O)R⁵, SO₂R⁵, C(O)R⁵, CO(O)R⁵, OC(O)R⁵, OC(O)OR⁵, NH₂, NHR⁵, N(R⁵)₂, NHC(O)R⁵, NR⁵C(O)R⁵, NHS(O)₂R⁵, NR⁵S(O)₂R⁵, NHC(O)OR⁵, NR⁵C(O)OR⁵, NHC(O)NH₂, NHC(O)NHR⁵, NHC(O)N(R⁵)₂, NR⁵C(O)NHR⁵, NR⁵C(O)N(R⁵)₂, C(O)NH₂, C(O)NHR⁵, C(O)N(R⁵)₂, C(O)NHOH, C(O)NHOR⁵, C(O)NHSO₂R⁵, C(O)NR⁵SO₂R⁵, SO₂NH₂, SO₂NHR⁵, SO₂N(R⁵)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁵, C(N)N(R⁵)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R³ aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁶, OR⁶, SR⁶, S(O)R⁶, SO₂R⁶, C(O)R⁶, CO(O)R⁶, OC(O)R⁶, OC(O)OR⁶, NH₂, NHR⁶, N(R⁶)₂, NHC(O)R⁶, NR⁶C(O)R⁶, NHS(O)₂R⁶, NR⁶S(O)₂R⁶, NHC(O)OR⁶, NR⁶C(O)OR⁶, NHC(O)NH₂, NHC(O)NHR⁶, NHC(O)N(R⁶)₂, NR⁶C(O)NHR⁶, NR⁶C(O)N(R⁶)₂, C(O)NH₂, C(O)NHR⁶, C(O)N(R⁶)₂, C(O)NHOH, C(O)NHOR⁶, C(O)NHSO₂R⁶, C(O)NR⁶SO₂R⁶, SO₂NH₂, SO₂NHR⁶, SO₂N(R⁶)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁶, C(N)N(R⁶)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I;

R⁵, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁵ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁸, OR⁸, SR⁸, S(O)R⁸, SO₂R⁸, NHR⁸, N(R⁸)₂, C(O)R⁸, C(O)NH₂, C(O)NHR⁸, C(O)N(R⁸)₂, NHC(O)R⁸, NR⁸C(O)R⁸, NHSO₂R⁸, NHC(O)OR⁸, SO₂NH₂, SO₂NHR⁸, SO₂N(R⁸)₂, NHC(O)NH₂, NHC(O)NHR⁸, OH, (O), C(O)OH, N₃, CN, NH₂, F, Cl, Br and I;

R⁶, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁶ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁹, OR⁹, SR⁹, S(O)R⁹, SO₂R⁹, NHR⁹, N(R⁹)₂, C(O)R⁹, C(O)NH₂, C(O)NHR⁹, C(O)N(R⁹)₂, NHC(O)R⁹, NR⁹C(O)R⁹, NHSO₂R⁹, NHC(O)OR⁹, SO₂NH₂, SO₂NHR⁹, SO₂N(R⁹)₂, NHC(O)NH₂, NHC(O)NHR⁹, OH, (O), C(O)OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br and I;

R⁷, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

R⁸, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

R⁹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

wherein the cyclic moieties represented by R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹ are independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, C(O)C(O)R¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, CF₃, OCF₃, F, Cl, Br and I;

R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, OR¹³, C(O)OR¹³, OCF₃, CF₃, F, Cl, Br and I;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; and

R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

with the proviso that when X¹ is CR¹ and X² is CR¹; R¹ is hydrogen; Y¹ is NHC(O); and R² is pyrrolyl; the R² pyrrolyl is not substituted with two alkyl groups.

In one embodiment of Formula (IVC), X¹ is N and X² is CR¹; or X¹ is CR¹ and X² is N; or X¹ is CR¹ and X² is CR¹. In another embodiment of Formula (IVC), X¹ is N and X² is CR¹. In another embodiment of Formula (IVC), X¹ is CR¹ and X² is N. In another embodiment of Formula (IVC), X¹ is CR¹ and X² is CR¹.

In one embodiment of Formula (IVC), Y¹ is C(O)NH, or NHC(O). In another embodiment of Formula (IVC), Y¹ is C(O)NH. In another embodiment of Formula (IVC), Y¹ is NHC(O).

In one embodiment of Formula (IVC), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I. In another embodiment of Formula (IVC), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, Cl, Br and I. In another embodiment of Formula (IVC), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, and Cl. In another embodiment of Formula (IVC), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is hydrogen.

In another aspect, the present invention provides compounds of Formula (IVD),

and pharmaceutically acceptable salts thereof; wherein R¹ and R² are as described herein for Formula (IC).

In one embodiment of Formula (IVC) and (IVD), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I. In another embodiment of Formula (IVC) and (IVD), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, Cl, Br and I. In another embodiment of Formula (IVC) and (IVD), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, and Cl. In another embodiment of Formula (IVC) and (IVD), R¹, at each occurrence, is hydrogen.

In one embodiment of Formula (IVC) and (IVD), R² is independently selected from the group consisting of C₄-C₆-alkyl, C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl, and 5-6 membered heteroaryl; wherein each R² C₄-C₆-alkyl, C₄-C₆-alkenyl, and C₄-C₆-alkynyl is substituted with one or more substituents independently selected from the group consisting of R³, OR³, SR³, S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂, NHR³, N(R³)₂, NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³, NR³C(O)OR³, NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³, NR³C(O)N(R³)₂, C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³, C(O)NHSO₂R³, C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I. In another embodiment of Formula (IVC) and (IVD), R² is aryl; wherein each R² aryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, C(O)NHR⁴, F, Cl, and I. In another embodiment of Formula (IVC) and (IVD), R² is aryl; wherein each R² aryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, C(O)NHR⁴, and F. In another embodiment of Formula (IVC) and (IVD), R² is phenyl; wherein each R² phenyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, C(O)NHR⁴, and F. In another embodiment of Formula (IVC) and (IVD), R² is phenyl; wherein each R² phenyl is substituted with one substituent independently selected from the group consisting of R⁴, OR⁴, and SO₂R⁴.

In another embodiment of Formula (IVC) and (IVD), R² is 5-6 membered heteroaryl; wherein each R² 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, C(O)NHR⁴, F, Cl, and I. In another embodiment of Formula (IVC) and (IVD), R² is 5-6 membered heteroaryl; wherein each R² 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, C(O)NHR⁴, and F. In another embodiment of Formula (IVC) and (IVD), R² is pyridinyl, furanyl, thiophenyl, pyrazole, or thiazolyl; wherein each R² pyridinyl, furanyl, thiophenyl, pyrazole, and thiazolyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, C(O)NHR⁴, and F.

In one embodiment of Formula (IVC) and (IVD), R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)R⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I. In another embodiment of Formula (IVC) and (IVD), R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl.

In one embodiment of Formula (IVC) and (IVD), each R⁴ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)R⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I. In another embodiment of Formula (IVC) and (IVD), each R⁴ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, N(R⁷)₂, F, Cl, Br and I.

In one embodiment of Formula (IVC) and (IVD), R⁷, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl. In another embodiment of Formula (IVC) and (IVD), R⁷, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl.

In one embodiment of Formula (IVC) and (IVD), each R⁴ and R⁷ cyclic moiety is independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, OR¹³, C(O)OR¹³, OCF₃, CF₃, F, Cl, Br and I; R¹², at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; and R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl.

In another embodiment of Formula (IVC) and (IVD), each R⁴ and R⁷ cyclic moiety is independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, C(O)C(O)R¹⁰, CO(O)H, OH, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl, are optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SO₂R¹¹, NH₂, N(R¹¹)₂, NHC(O)R¹¹, NHS(O)₂R¹¹, OH, NO₂, and F; wherein each R¹⁰ aryl, heterocyclyl and cycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², C(O)R¹², NH₂, OH, CN, CF₃, OCF₃, F, and Cl; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹¹ alkyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, CF₃, F, and Cl; R¹², at each occurrence, is independently selected from the group consisting of alkyl and aryl; and R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, and cycloalkyl.

One embodiment of this invention pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (IVC)

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is C(O)NH, or NHC(O);

R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, Cl, and F;

R² is aryl or 5-6 membered heteroaryl wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, SO₂R⁴, OR⁴, C(O)NHR⁴, and F;

R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, and cycloalkyl; wherein each R⁴ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, N(R⁷)₂, and F;

R⁷, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl;

wherein the cyclic moieties represented by R⁴ and R⁷ are independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, C(O)R¹⁰, C(O)C(O)R¹⁰, CO(O)R¹⁰, C(O)OH, OH and F;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, SO₂R¹¹, NH₂, N(R¹¹)₂, NHC(O)R¹¹, NHS(O)₂R¹¹, OH, NO₂, and F; wherein each R¹⁰ aryl, heterocyclyl and cycloalkyl is optionally substituted with one or more R¹², OR¹², C(O)R¹², NH₂, OH, CN, CF₃, OCF₃, F, and Cl;

R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹¹ alkyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, C(O)OR¹³, OCF₃, CF₃, F, and Cl;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, and aryl; and

R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, cycloalkyl, and heterocyclyl;

with the proviso that when X¹ is CR¹ and X² is CR¹; R¹ is hydrogen; Y¹ is NHC(O); and R² is pyrrolyl; the R² pyrrolyl is not substituted with two alkyl groups.

Still another embodiment pertains to compounds having Formula (IV), which include

-   tert-butyl     4-[4-({[(3S)-1-(pyridin-3-yl)pyrrolidin-3-yl]carbonyl}amino)phenoxy]piperidine-1-carboxylate; -   tert-butyl     4-[4-({[(3R)-1-(pyridin-3-yl)pyrrolidin-3-yl]carbonyl}amino)phenoxy]piperidine-1-carboxylate; -   (3S)-1-(pyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridin-3-yl)-N-[4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]pyrrolidine-3-carboxamide; -   (3S)-1-(pyridin-3-yl)-N-[4-({1-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]pyrrolidine-3-carboxamide; -   (3S)-1-(pyridin-3-yl)-N-(4-{[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridin-3-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxy}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}     oxy)phenyl]-1-(pyridin-3-yl)pyrrolidine-3-carboxamide; -   tert-butyl     4-(4-{[(3S)-1-(pyridin-3-yl)pyrrolidin-3-yl]carbamoyl}phenoxy)piperidine-1-carboxylate; -   tert-butyl     4-(4-{[(3R)-1-(pyridin-3-yl)pyrrolidin-3-yl]carbamoyl}phenoxy)piperidine-1-carboxylate; -   (3S)—N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide;     and pharmaceutically acceptable salts thereof -   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[(1-benzoylpiperidin-4-yl)sulfonyl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-fluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylcarbonyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[(3R)-1-(5,6-dichloropyridazin-4-yl)pyrrolidin-3-yl]-5[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide; -   N-[(3R)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide; -   N-[(3S)-1-(5,6-dichloropyridazin-4-yl)pyrrolidin-3-yl]-5[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide; -   N-[(3S)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]-5[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide; -   N-[(3R)-1-(5,6-dichloropyridazin-4-yl)pyrrolidin-3-yl]-5[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-3-carboxamide; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3R)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-3-carboxamide; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3R)-1-(pyridazin-4-yl)pyrrolidin-3-yl]thiophene-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)piperidine-4-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)piperidine-4-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidi4-yl]phenyl}-1-(pyridazin-3-yl)piperidine-4-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}piperidine-4-carboxamide; -   N-[(3S)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]-5[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(1,3-thiazol-5-ylcarbonyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2S)-2-phenylbutanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2S)-2-methoxy-2-phenylacetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2R)-2-methoxy-2-phenylacetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(ethoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(4-methylphenoxy)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(naphthalen-1-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2,6-dichlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(naphthalen-1-ylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-(4-{1-[4-(thiophen-2-yl)butanoyl]piperidin-4-yl}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,5-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(naphthalen-2-ylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[3-(phenylsulfonyl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-[4-(1-{[3-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)phenyl]pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(furan-2-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(N-benzoylglycyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2,4-dichlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(1-methylcyclohexyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(6-methylpyridin-3-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(3-chlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-propanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclopentylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclopropylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-fluoro-5-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(5-fluoropyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(2-fluoro-6-methylpyridin-3-yl)azetidine-3-carboxamide; -   (3S)—N-{4-[1-(2-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,4-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-heptanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,4-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(4-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,3-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-hexanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-butanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(3,5-dimethylphenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3,5-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-fluoro-2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(4-chlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(furan-3-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3,4-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[2-chloro-5-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-acetylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3,5-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-ethoxypropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,5-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,5-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(5-fluoro-2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(diphenylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-(4-{1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(pent-4-enoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-(4-{1-[3-(trifluoromethoxy)benzoyl]piperidin-4-yl}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(1-phenylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[2-fluoro-5-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclohexylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-methoxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-ethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-tert-butylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-(4-{1-[3-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(pent-4-ynoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(3-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[3-(methylsulfanyl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(1-acetylpiperidin-4-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(but-3-enoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-fluoro-4-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-methoxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2-chlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(N-acetyl-L-leucyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-cyanobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-methoxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,3-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[4-(propan-2-yl)benzoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclohexylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-hydroxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-cyanobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(2-cyanopyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(4-cyanopyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-fluoro-4-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(5-cyanopyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(5-methylpyridin-3-yl)azetidine-3-carboxamide; -   2-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]-1,3-thiazole-5-carboxamide; -   (3S)—N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(2-methylpyridin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(2-methylpyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   N-[(3S)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]furan-2-carboxamide; -   5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]furan-2-carboxamide; -   N-(4-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[(3S)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]-4-[1-(2-methylpropanoyl)piperidin-4-yl]benzamide; -   N-(4-{1-[2-(piperazin-1-yl)ethyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   4-[1-(2-methylpropanoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]benzamide; -   N-{4-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   5-[1-(3-fluorobenzoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-[1-(4-fluorobenzoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   (3S)—N-(4-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]-5[1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]thiophene-2-carboxamide; -   (3S)—N-{4-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   5-[1-(2-methylpropanoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-{1[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-(1-benzoylpiperidin-4-yl)-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]-5[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]thiophene-2-carboxamide; -   N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]-5-{1[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}thiophene-2-carboxamide; -   5-{1-[(1-methylpiperidin-4-yl)acetyl]piperidin-4-yl}-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]-5-[1-(1,3-thiazol-4-ylcarbonyl)piperidin-4-yl]thiophene-2-carboxamide; -   (3S)—N-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(propan-2-yl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclopropylmethyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-2-ylmethyl)-1H-pyrazol-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-tert-butyl-1H-pyrazol-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-benzoylpyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-(2-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-(3-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-(4-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-(2-methylbenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-({(3R)-1-[(4,4-difluorocyclohexyl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(4,4,4-trifluorobutanoyl)pyrrolidin-3-yl]oxy}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-[4-(5-propyl-1,2,4-oxadiazol-3-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   (3S)—N-{4-[1-(2-fluorobenzoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-fluorobenzoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-fluorobenzoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-benzoylazetidin-3-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,2-dimethylpropanoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3,5-difluorobenzoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-methylbenzoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,4-difluorobenzoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3R)—N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3R)—N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3R)—N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(cyclohexylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(3-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[(1-benzoylpiperidin-4-yl)oxy]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(4-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-({1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-{4-[5-(2,2-dimethylpropyl)-1,3,4-oxadiazol-2-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropyl)-1H-imidazol-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[5-(2,2-dimethylpropyl)-1,2,4-oxadiazol-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[3-cyclopropyl-1-(2-methoxyethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   tert-butyl     4-(5-{[1-(pyridazin-3-yl)azetidin-3-yl]carbamoyl}thiophen-2-yl)piperidine-1-carboxylate; -   tert-butyl     4-fluoro-4-[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]piperidine-1-carboxylate; -   5-(1-benzoylpiperidin-4-yl)-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2-methylbenzoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   5-[1-(3-fluorobenzoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   5-[1-(4-fluorobenzoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   5-[1-(3,5-difluorobenzoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   N-{4-[3-cyclopropyl-1-(2-hydroxyethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   1-(6-fluoropyridazin-3-yl)-N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(2-ethylbutanoyl)piperidin-4-yl]phenyl}-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   (3S)—N-(4-{[(3S)-1-benzoylpyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3S)-1-(2-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3S)-1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3S)-1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-{2-fluoro-4[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)-2-fluorophenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   (3S)—N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[(1-benzoylpiperidin-4-yl)oxy]phenyl}-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(cyclohexylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-{4[8-(2-methylpropanoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4[8-(4,4,4-trifluorobutanoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}azetidine-3-carboxamide; -   N-[4-(8-benzoyl-8-azabicyclo[3.2.1]oct-3-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[8-(2-fluorobenzoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4[8-(2,2-dimethylpropanoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{8-[(1-methylcyclopropyl)carbonyl]-8-azabicyclo[3.2.1]oct-3-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methoxyethyl)-3-(2-methylpropyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   5-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   5-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   N-[1-(pyridazin-3-yl)azetidin-3-yl]-5-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]thiophene-2-carboxamide; -   5-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   benzyl     4-[4-({[1-(6-chloropyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-4-fluoropiperidine-1-carboxylate; -   benzyl     4-[4-({[1-(6-chloropyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-4-hydroxypiperidine-1-carboxylate; -   N-[1-(pyridazin-3-yl)azetidin-3-yl]-5-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]thiophene-2-carboxamide; -   5-[1-(cyclopropylcarbonyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   N-{4-[4-fluoro-1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylcarbonyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(2-fluoro-4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoyl-4-fluoropiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)-4-fluoropiperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4[3-tert-butyl-1-(2-methoxyethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-butyl-3-tert-butyl-1H-pyrazol-5-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[3-tert-butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)-2-fluorophenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   (3S)—N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]furan-2-carboxamide; -   (3S)—N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(4-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(4-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   5-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]-5-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]thiophene-2-carboxamide; -   5-[1-(cyclopropylacetyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide; -   5-[1-(bicyclo[2.2.1]hept-2-ylacetyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide;     and pharmaceutically acceptable salts thereof.

Embodiments of Formula (VC)

In another aspect, the present invention provides compounds of Formula (VC)

and pharmaceutically acceptable salts thereof; wherein X¹, X², R¹, and Y¹ are as described in Formula (IC) herein and R^(4x) is as described herein for substituents on R² when R² is aryl in Formula (IC).

One embodiment of this invention pertains to compounds of Formula (VC) or pharmaceutically acceptable salts thereof;

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is C(O)NH, or NHC(O);

R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I;

R^(4X) is independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I;

R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I;

R⁷, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl;

wherein the cyclic moieties represented by R⁴, and R⁷, are independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, C(O)C(O)R¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, CF₃, OCF₃, F, Cl, Br and I;

R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, OR¹³, C(O)OR¹³, OCF₃, CF₃, F, Cl, Br and I;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; and

R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl.

In one embodiment of Formula (VC), X¹ is N and X² is CR¹; or X¹ is CR¹ and X² is N; or X¹ is CR¹ and X² is CR¹. In another embodiment of Formula (VC), X¹ is N and X² is CR¹. In another embodiment of Formula (VC), X¹ is CR¹ and X² is N. In another embodiment of Formula (VC), X¹ is CR¹ and X² is CR¹.

In one embodiment of Formula (VC), Y¹ is C(O)NH, or NHC(O). In another embodiment of Formula (VC), Y¹ is C(O)NH. In another embodiment of Formula (VC), Y¹ is NHC(O).

In one embodiment of Formula (VC), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I. In another embodiment of Formula (VC), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, Cl, Br and I. In another embodiment of Formula (VC), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, and Cl. In another embodiment of Formula (VC), X¹ is CR¹ and X² is CR¹; and R¹, at each occurrence, is hydrogen.

In another aspect, the present invention provides compounds of Formula (VD),

and pharmaceutically acceptable salts thereof; wherein R¹ is described herein for Formula (IC) and R^(4x) is as described herein for substituents on R² when R² is aryl in Formula (IC).

In one embodiment of Formula (VC) and (VD), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I. In another embodiment of Formula (VC) and (VD), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, Cl, Br and I. In another embodiment of Formula (VC) and (VD), R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, F, and Cl. In another embodiment of Formula (VC) and (VD), R¹, at each occurrence, is hydrogen.

In one embodiment of Formula (VC) and (VD), R^(4X) is independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, and I. In another embodiment of Formula (VC) and (VD), R^(4X) is independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, C(O)NHR⁴, F, Cl, and I. In another embodiment of Formula (VC) and (VD), R^(4X) is independently selected from the group consisting of R⁴, OR⁴, SO₂R⁴, C(O)NHR⁴, and F.

In one embodiment of Formula (VC) and (VD), R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I. In another embodiment of Formula (VC) and (VD), R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl.

In one embodiment of Formula (VC) and (VD), each R⁴ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I. In another embodiment of Formula (VC) and (VD), each R⁴ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, N(R⁷)₂, F, Cl, Br and I.

In one embodiment of Formula (VC) and (VD), R⁷, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl. In another embodiment of Formula (VC) and (VD), R⁷, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl.

In one embodiment of Formula (VC) and (VD), each R⁴ and R⁷ cyclic moiety is independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, OR¹³, C(O)OR¹³, OCF₃, CF₃, F, Cl, Br and I; R¹², at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; and R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl.

In another embodiment of Formula (VC) and (VD), each R⁴ and R⁷ cyclic moiety is independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, C(O)C(O)R¹⁰, CO(O)H, OH, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl, are optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, SO₂R¹¹, NH₂, N(R¹¹)₂, NHC(O)R¹¹, NHS(O)₂R¹¹, OH, NO₂, and F; wherein each R¹⁰ aryl, heterocyclyl and cycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², C(O)R¹², NH₂, OH, CN, CF₃, OCF₃, F, and Cl; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹¹ alkyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, CF₃, F, and Cl; R¹², at each occurrence, is independently selected from the group consisting of alkyl and aryl; and R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, and cycloalkyl.

One embodiment of this invention pertains to compounds or pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds having Formula (VC)

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is C(O)NH, or NHC(O);

R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, alkoxy, CN, Cl, and F;

R^(4X) is independently selected from the group consisting of R⁴, SO₂R⁴, OR⁴, and F;

R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, aryl, heterocyclyl, and cycloalkyl; wherein each R⁴ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, N(R⁷)₂, and F;

R⁷, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl;

wherein the cyclic moieties represented by R⁴ and R⁷ are independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, C(O)R¹⁰, C(O)C(O)R¹⁰, CO(O)R¹⁰, C(O)OH, OH and F;

R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, SO₂R¹¹, NH₂, N(R¹¹)₂, NHC(O)R¹¹, NHS(O)₂R¹¹, OH, NO₂, and F; wherein each R¹⁰ aryl, heterocyclyl and cycloalkyl is optionally substituted with one or more R¹², OR¹², C(O)R¹², NH₂, OH, CN, CF₃, OCF₃, F, and Cl;

R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹¹ alkyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, C(O)OR¹³, OCF₃, CF₃, F, and Cl;

R¹², at each occurrence, is independently selected from the group consisting of alkyl, and aryl; and

R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, cycloalkyl, and heterocyclyl.

Still another embodiment pertains to compounds having Formula (VC), which include

-   tert-butyl     4-[4-({[(3S)-1-(pyridin-3-yl)pyrrolidin-3-yl]carbonyl}amino)phenoxy]piperidine-1-carboxylate; -   tert-butyl     4-[4-({[(3R)-1-(pyridin-3-yl)pyrrolidin-3-yl]carbonyl}amino)phenoxy]piperidine-1-carboxylate; -   (3S)-1-(pyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridin-3-yl)-N-[4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]pyrrolidine-3-carboxamide; -   (3S)-1-(pyridin-3-yl)-N-[4-({1-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]pyrrolidine-3-carboxamide; -   (3S)-1-(pyridin-3-yl)-N-(4-{[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridin-3-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxy}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}     oxy)phenyl]-1-(pyridin-3-yl)pyrrolidine-3-carboxamide; -   tert-butyl     4-(4-{[(3S)-1-(pyridin-3-yl)pyrrolidin-3-yl]carbamoyl}phenoxy)piperidine-1-carboxylate; -   tert-butyl     4-(4-{[(3R)-1-(pyridin-3-yl)pyrrolidin-3-yl]carbamoyl}phenoxy)piperidine-1-carboxylate; -   (3S)—N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide;     and pharmaceutically acceptable salts thereof -   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[(1-benzoylpiperidin-4-yl)sulfonyl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(4-fluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-(4-{[1-(cyclopentylcarbonyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)piperidine-4-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)piperidine-4-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidi4-yl]phenyl}-1-(pyridazin-3-yl)piperidine-4-carboxamide; -   1-(pyridazin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}piperidine-4-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(1,3-thiazol-5-ylcarbonyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2S)-2-phenylbutanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2S)-2-methoxy-2-phenylacetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2R)-2-methoxy-2-phenylacetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(ethoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(4-methylphenoxy)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(naphthalen-1-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2,6-dichlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(naphthalen-1-ylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-(4-{1-[4-(thiophen-2-yl)butanoyl]piperidin-4-yl}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,5-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(naphthalen-2-ylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[3-(phenylsulfonyl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-[4-(1-{[3-(trifluoromethyl)phenyl]acetyl}piperidin-4-yl)phenyl]pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(furan-2-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(N-benzoylglycyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2,4-dichlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(1-methylcyclohexyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(6-methylpyridin-3-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(3-chlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-propanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclopentylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclopropylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-fluoro-5-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(5-fluoropyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(2-fluoro-6-methylpyridin-3-yl)azetidine-3-carboxamide; -   (3S)—N-{4-[1-(2-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,4-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-heptanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,4-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(4-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,3-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-hexanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-butanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-methylpentanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(3,5-dimethylphenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3,5-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-fluoro-2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(4-chlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(furan-3-ylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3,4-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[2-chloro-5-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-acetylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3,5-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-ethoxypropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,5-dichlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,5-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(5-fluoro-2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(diphenylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-(4-{1-[4-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(pent-4-enoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-(4-{1-[3-(trifluoromethoxy)benzoyl]piperidin-4-yl}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(1-phenylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[2-fluoro-5-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclohexylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-methoxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-ethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-tert-butylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-(4-{1-[3-(trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(pent-4-ynoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(3-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[3-(methylsulfanyl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(1-acetylpiperidin-4-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(but-3-enoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-fluoro-4-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-methoxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2-chlorophenyl)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(N-acetyl-L-leucyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-cyanobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-methoxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,3-dimethylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{1-[4-(propan-2-yl)benzoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclohexylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-hydroxybenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-cyanobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(2-cyanopyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(4-cyanopyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-fluoro-4-methylpyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(5-cyanopyridin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(5-methylpyridin-3-yl)azetidine-3-carboxamide; -   (3S)—N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(2-methylpyridin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(2-methylpyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide; -   N-(4-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[(3S)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]-4-[1-(2-methylpropanoyl)piperidin-4-yl]benzamide; -   N-(4-{1-[2-(piperazin-1-yl)ethyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   4-[1-(2-methylpropanoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]benzamide; -   N-{4-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   (3S)—N-(4-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(propan-2-yl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(cyclopropylmethyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-2-ylmethyl)-1H-pyrazol-4-yl]phenyl}pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-tert-butyl-1H-pyrazol-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-benzoylpyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-(2-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-(3-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-(4-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-(2-methylbenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-({(3R)-1-[(4,4-difluorocyclohexyl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)-1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(4,4,4-trifluorobutanoyl)pyrrolidin-3-yl]oxy}phenyl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3R)-1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-[4-(5-propyl-1,2,4-oxadiazol-3-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   (3S)—N-{4-[1-(2-fluorobenzoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3-fluorobenzoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(4-fluorobenzoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-benzoylazetidin-3-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,2-dimethylpropanoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(3,5-difluorobenzoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2-methylbenzoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,4-difluorobenzoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3R)—N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3R)—N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3R)-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(cyclohexylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(3-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[(1-benzoylpiperidin-4-yl)oxy]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(4-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-({1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}oxy)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-{4-[5-(2,2-dimethylpropyl)-1,3,4-oxadiazol-2-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropyl)-1H-imidazol-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[5-(2,2-dimethylpropyl)-1,2,4-oxadiazol-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[3-cyclopropyl-1-(2-methoxyethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   tert-butyl     4-(5-{[1-(pyridazin-3-yl)azetidin-3-yl]carbamoyl}thiophen-2-yl)piperidine-1-carboxylate; -   tert-butyl     4-fluoro-4-[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]piperidine-1-carboxylate; -   5-(1-benzoylpiperidin-4-yl)-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2-methylbenzoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   5-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   5-[1-(3-fluorobenzoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   5-[1-(4-fluorobenzoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   5-[1-(3,5-difluorobenzoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   N-{4-[3-cyclopropyl-1-(2-hydroxyethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   1-(6-fluoropyridazin-3-yl)-N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide; -   N-{4-[1-(2-ethylbutanoyl)piperidin-4-yl]phenyl}-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide; -   (3S)—N-(4-{[(3S)-1-benzoylpyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3S)-1-(2-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3S)-1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[(3S)-1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-{2-fluoro-4[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)-2-fluorophenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(2-methylbenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   (3S)—N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[(1-benzoylpiperidin-4-yl)oxy]phenyl}-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-(4-{[1-(cyclohexylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   N-{4[8-(2-methylpropanoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   1-(pyridazin-3-yl)-N-{4[8-(4,4,4-trifluorobutanoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}azetidine-3-carboxamide; -   N-[4-(8-benzoyl-8-azabicyclo[3.2.1]oct-3-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[8-(2-fluorobenzoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4[8-(2,2-dimethylpropanoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(4-{8-[(1-methylcyclopropyl)carbonyl]-8-azabicyclo[3.2.1]oct-3-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2-methoxyethyl)-3-(2-methylpropyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   5-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   5-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   N-[1-(pyridazin-3-yl)azetidin-3-yl]-5-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]thiophene-2-carboxamide; -   5-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide; -   benzyl     4-[4-({[1-(6-chloropyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-4-fluoropiperidine-1-carboxylate; -   benzyl     4-[4-({[1-(6-chloropyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-4-hydroxypiperidine-1-carboxylate; -   N-[1-(pyridazin-3-yl)azetidin-3-yl]-5-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]thiophene-2-carboxamide; -   5-[1-(cyclopropylcarbonyl)piperidin-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide; -   N-{4-[4-fluoro-1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylcarbonyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-(2-fluoro-4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoyl-4-fluoropiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)-4-fluoropiperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4[3-tert-butyl-1-(2-methoxyethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-[4-(1-butyl-3-tert-butyl-1H-pyrazol-5-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{4[3-tert-butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-[4-(1-benzoylpiperidin-4-yl)-2-fluorophenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   N-{2-fluoro-4[1-(4,4,4-tri     fluorobutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide; -   (3S)—N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(4-methylpyridazin-3-yl)pyrrolidine-3-carboxamide; -   (3S)—N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(4-methylpyridazin-3-yl)pyrrolidine-3-carboxamide;     and pharmaceutically acceptable salts thereof.

Pharmaceutical Compositions, Combination Therapies, Methods of Treatment, and Administration

Another embodiment comprises pharmaceutical compositions comprising a compound having Formula (I) and an excipient.

Still another embodiment comprises methods of treating cancer in a mammal comprising administering thereto a therapeutically acceptable amount of a compound having Formula (I).

Still another embodiment pertains to compositions for treating diseases during which NAMPT is expressed, said compositions comprising an excipient and a therapeutically effective amount of the compound having Formula (I).

Still another embodiment pertains to methods of treating disease in a patient during which NAMPT is expressed, said methods comprising administering to the patient a therapeutically effective amount of a compound having Formula (I).

Still another embodiment pertains to compositions for treating inflammatory and tissue repair disorders; particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, particularly wherein the cancer is selected from breast, prostate, lung, colon, cervix, ovary, skin, CNS, bladder, pancreas, leukemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia, said compositions comprising an excipient and a therapeutically effective amount of the compound having Formula (I).

Still another embodiment pertains to methods of treating inflammatory and tissue repair disorders; particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, particularly wherein the cancer is selected from breast, prostate, lung, colon, cervix, ovary, skin, CNS, bladder, pancreas, leukemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia in a patient, said methods comprising administering to the patient a therapeutically effective amount of a compound having Formula (I).

Still another embodiment pertains to compositions for treating diseases during which NAMPT is expressed, said compositions comprising an excipient and a therapeutically effective amount of the compound having Formula (I) and a therapeutically effective amount of one additional therapeutic agent or more than one additional therapeutic agent.

Still another embodiment pertains to methods of treating disease in a patient during which NAMPT is expressed, said methods comprising administering to the patient a therapeutically effective amount of a compound having Formula (I) and a therapeutically effective amount of one additional therapeutic agent or more than one additional therapeutic agent.

Still another embodiment pertains to compositions for treating inflammatory and tissue repair disorders; particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, particularly wherein the cancer is selected from breast, prostate, lung, colon, cervix, ovary, skin, CNS, bladder, pancreas, leukemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia, said compositions comprising an excipient and a therapeutically effective amount of the compound having Formula (I) and a therapeutically effective amount of one additional therapeutic agent or more than one additional therapeutic agent.

Still another embodiment pertains to methods of treating inflammatory and tissue repair disorders; particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, particularly wherein the cancer is selected from breast, prostate, lung, colon, cervix, ovary, skin, CNS, bladder, pancreas, leukemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia in a patient, said methods comprising administering to the patient a therapeutically effective amount of the compound having Formula (I) and a therapeutically effective amount of one additional therapeutic agent or more than one additional therapeutic agent.

Metabolites of compounds having Formula (I), produced by in vitro or in vivo metabolic processes, may also have utility for treating diseases associated with NAMPT.

Certain precursor compounds which may be metabolized in vitro or in vivo to form compounds having Formula (I) may also have utility for treating diseases associated with NAMPT.

Compounds having Formula (I) may exist as acid addition salts, basic addition salts or zwitterions. Salts of the compounds are prepared during isolation or following purification of the compounds. Acid addition salts of the compounds are those derived from the reaction of the compounds with an acid. For example, the acetate, adipate, alginate, bicarbonate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, camphorsufonate, digluconate, formate, fumarate, glycerophosphate, glutamate, hemisulfate, heptanoate, hexanoate, hydrochloride, hydrobromide, hydroiodide, lactobionate, lactate, maleate, mesitylenesulfonate, methanesulfonate, naphthylenesulfonate, nicotinate, oxalate, pamoate, pectinate, persulfate, phosphate, picrate, propionate, succinate, tartrate, thiocyanate, trichloroacetic, trifluoroacetic, para-toluenesulfonate, and undecanoate salts of the compounds are contemplated as being embraced by this invention. Basic addition salts of the compounds are those derived from the reaction of the compounds with the hydroxide, carbonate or bicarbonate of cations such as lithium, sodium, potassium, calcium, and magnesium.

The compounds having Formula (I) may be administered, for example, bucally, ophthalmically, orally, osmotically, parenterally (intramuscularly, intraperitoneally intrasternally, intravenously, subcutaneously), rectally, topically, transdermally or vaginally.

Therapeutically effective amounts of compounds having Formula (I) depend on the recipient of the treatment, the disorder being treated and the severity thereof, the composition containing the compound, the time of administration, the route of administration, the duration of treatment, the compound potency, its rate of clearance and whether or not another drug is co-administered. The amount of a compound of this invention having Formula (I) used to make a composition to be administered daily to a patient in a single dose or in divided doses is from about 0.03 to about 200 mgkg body weight. Single dose compositions contain these amounts or a combination of submultiples thereof.

Compounds having Formula (I) may be administered with or without an excipient. Excipients include, for example, encapsulating materials or additives such as absorption accelerators, antioxidants, binders, buffers, coating agents, coloring agents, diluents, disintegrating agents, emulsifiers, extenders, fillers, flavoring agents, humectants, lubricants, perfumes, preservatives, propellants, releasing agents, sterilizing agents, sweeteners, solubilizers, wetting agents and mixtures thereof.

Excipients for preparation of compositions comprising a compound having Formula (I) to be administered orally in solid dosage form include, for example, agar, alginic acid, aluminum hydroxide, benzyl alcohol, benzyl benzoate, 1,3-butylene glycol, carbomers, castor oil, cellulose, cellulose acetate, cocoa butter, corn starch, corn oil, cottonseed oil, cross-povidone, diglycerides, ethanol, ethyl cellulose, ethyl laureate, ethyl oleate, fatty acid esters, gelatin, germ oil, glucose, glycerol, groundnut oil, hydroxypropylmethyl cellulose, isopropanol, isotonic saline, lactose, magnesium hydroxide, magnesium stearate, malt, mannitol, monoglycerides, olive oil, peanut oil, potassium phosphate salts, potato starch, povidone, propylene glycol, Ringer's solution, safflower oil, sesame oil, sodium carboxymethyl cellulose, sodium phosphate salts, sodium lauryl sulfate, sodium sorbitol, soybean oil, stearic acids, stearyl fumarate, sucrose, surfactants, talc, tragacanth, tetrahydrofurfuryl alcohol, triglycerides, water, and mixtures thereof. Excipients for preparation of compositions comprising a compound of this invention having Formula (I) to be administered ophthalmically or orally in liquid dosage forms include, for example, 1,3-butylene glycol, castor oil, corn oil, cottonseed oil, ethanol, fatty acid esters of sorbitan, germ oil, groundnut oil, glycerol, isopropanol, olive oil, polyethylene glycols, propylene glycol, sesame oil, water and mixtures thereof. Excipients for preparation of compositions comprising a compound of this invention having Formula (I) to be administered osmotically include, for example, chlorofluorohydrocarbons, ethanol, water and mixtures thereof. Excipients for preparation of compositions comprising a compound of this invention having Formula (I) to be administered parenterally include, for example, 1,3-butanediol, castor oil, corn oil, cottonseed oil, dextrose, germ oil, groundnut oil, liposomes, oleic acid, olive oil, peanut oil, Ringer's solution, safflower oil, sesame oil, soybean oil, U.S.P. or isotonic sodium chloride solution, water and mixtures thereof. Excipients for preparation of compositions comprising a compound of this invention having Formula (I) to be administered rectally or vaginally include, for example, cocoa butter, polyethylene glycol, wax and mixtures thereof.

Compounds having Formula (I) are expected to be useful when used with alkylating agents, angiogenesis inhibitors, antibodies, antimetabolites, antimitotics, antiproliferatives, antivirals, aurora kinase inhibitors, apoptosis promoters (for example, Bcl-xL, Bcl-w and Bfl-1) inhibitors, activators of death receptor pathway, Bcr-Abl kinase inhibitors, BiTE (Bi-Specific T cell Engager) antibodies, antibody drug conjugates, biologic response modifiers, cyclin-dependent kinase inhibitors, cell cycle inhibitors, cyclooxygenase-2 inhibitors, DVDs, leukemia viral oncogene homolog (ErbB2) receptor inhibitors, growth factor inhibitors, heat shock protein (HSP)-90 inhibitors, histone deacetylase (HDAC) inhibitors, hormonal therapies, immunologicals, inhibitors of inhibitors of apoptosis proteins (IAPs), intercalating antibiotics, kinase inhibitors, kinesin inhibitors, Jak2 inhibitors, mammalian target of rapamycin inhibitors, microRNA's, mitogen-activated extracellular signal-regulated kinase inhibitors, multivalent binding proteins, non-steroidal anti-inflammatory drugs (NSAIDs), poly ADP (adenosine diphosphate)-ribose polymerase (PARP) inhibitors, platinum chemotherapeutics, polo-like kinase (Plk) inhibitors, phosphoinositide-3 kinase (PI3K) inhibitors, proteosome inhibitors, purine analogs, pyrimidine analogs, receptor tyrosine kinase inhibitors, retinoidsdeltoids plant alkaloids, small inhibitory ribonucleic acids (siRNAs), topoisomerase inhibitors, ubiquitin ligase inhibitors, and the like, and in combination with one or more of these agents.

BiTE antibodies are bi-specific antibodies that direct T-cells to attack cancer cells by simultaneously binding the two cells. The T-cell then attacks the target cancer cell. Examples of BiTE antibodies include adecatumumab (Micromet MT201), blinatumomab (Micromet MT103) and the like. Without being limited by theory, one of the mechanisms by which T-cells elicit apoptosis of the target cancer cell is by exocytosis of cytolytic granule components, which include perforin and granzyme B.

SiRNAs are molecules having endogenous RNA bases or chemically modified nucleotides. The modifications do not abolish cellular activity, but rather impart increased stability and/or increased cellular potency. Examples of chemical modifications include phosphorothioate groups, 2′-deoxynucleotide, 2′-OCH₃-containing ribonucleotides, 2′-F-ribonucleotides, 2′-methoxyethyl ribonucleotides, combinations thereof and the like. The siRNA can have varying lengths (e.g., 10-200 bps) and structures (e.g., hairpins, singledouble strands, bulges, nicksgaps, mismatches) and are processed in cells to provide active gene silencing. A double-stranded siRNA (dsRNA) can have the same number of nucleotides on each strand (blunt ends) or asymmetric ends (overhangs). The overhang of 1-2 nucleotides can be present on the sense and/or the antisense strand, as well as present on the 5′- and or the 3′-ends of a given strand.

Multivalent binding proteins are binding proteins comprising two or more antigen binding sites. Multivalent binding proteins are engineered to have the three or more antigen binding sites and are generally not naturally occurring antibodies. The term “multispecific binding protein” means a binding protein capable of binding two or more related or unrelated targets. Dual variable domain (DVD) binding proteins are tetravalent or multivalent binding proteins binding proteins comprising two or more antigen binding sites. Such DVDs may be monospecific (i.e., capable of binding one antigen) or multispecific (i.e., capable of binding two or more antigens). DVD binding proteins comprising two heavy chain DVD polypeptides and two light chain DVD polypeptides are referred to as DVD Ig's. Each half of a DVD Ig comprises a heavy chain DVD polypeptide, a light chain DVD polypeptide, and two antigen binding sites. Each binding site comprises a heavy chain variable domain and a light chain variable domain with a total of 6 CDRs involved in antigen binding per antigen binding site.

Alkylating agents include altretamine, AMD-473, AP-5280, apaziquone, bendamustine, brostallicin, busulfan, carboquone, carmustine (BCNU), chlorambucil, CLORETAZINE® (laromustine, VNP 40101M), cyclophosphamide, decarbazine, estramustine, fotemustine, glufosfamide, ifosfamide, KW-2170, lomustine (CCNU), mafosfamide, melphalan, mitobronitol, mitolactol, nimustine, nitrogen mustard N-oxide, ranimustine, temozolomide, thiotepa, TREANDA® (bendamustine), treosulfan, trofosfamide and the like.

Angiogenesis inhibitors include endothelial-specific receptor tyrosine kinase (Tie-2) inhibitors, epidermal growth factor receptor (EGFR) inhibitors, insulin growth factor-2 receptor (IGFR-2) inhibitors, matrix metalloproteinase-2 (MMP-2) inhibitors, matrix metalloproteinase-9 (MMP-9) inhibitors, platelet-derived growth factor receptor (PDGFR) inhibitors, thrombospondin analogs, vascular endothelial growth factor receptor tyrosine kinase (VEGFR) inhibitors and the like.

Antimetabolites include ALIMTA® (pemetrexed disodium, LY231514, MTA), 5-azacitidine, XELODA® (capecitabine), carmofur, LEUSTAT® (cladribine), clofarabine, cytarabine, cytarabine ocfosfate, cytosine arabinoside, decitabine, deferoxamine, doxifluridine, eflornithine, EICAR (5-ethynyl-1-(3-D-ribofuranosylimidazole-4-carboxamide), enocitabine, ethnylcytidine, fludarabine, 5-fluorouracil alone or in combination with leucovorin, GEMZAR® (gemcitabine), hydroxyurea, ALKERAN®(melphalan), mercaptopurine, 6-mercaptopurine riboside, methotrexate, mycophenolic acid, nelarabine, nolatrexed, ocfosfate, pelitrexol, pentostatin, raltitrexed, Ribavirin, triapine, trimetrexate, S-1, tiazofurin, tegafur, TS-1, vidarabine, UFT and the like.

Antivirals include ritonavir, hydroxychloroquine and the like.

Aurora kinase inhibitors include ABT-348, AZD-1152, MLN-8054, VX-680, Aurora A-specific kinase inhibitors, Aurora B-specific kinase inhibitors and pan-Aurora kinase inhibitors and the like.

Bcl-2 protein inhibitors include AT-101 ((−)gossypol), GENASENSE® (G3139 or oblimersen (Bcl-2-targeting antisense oligonucleotide)), IPI-194, IPI-565, N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide) (ABT-737), N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-en-1-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(morpholin-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzenesulfonamide (ABT-263), GX-070 (obatoclax) and the like.

Bcr-Abl kinase inhibitors include DASATINIB® (BMS-354825), GLEEVEC® (imatinib) and the like.

CDK inhibitors include AZD-5438, BMI-1040, BMS-032, BMS-387, CVT-2584, flavopyridol, GPC-286199, MCS-5A, PD0332991, PHA-690509, seliciclib (CYC-202, R-roscovitine), ZK-304709 and the like.

COX-2 inhibitors include ABT-963, ARCOXIA® (etoricoxib), BEXTRA® (valdecoxib), BMS347070, CELEBREX® (celecoxib), COX-189 (lumiracoxib), CT-3, DERAMAXX® (deracoxib), JTE-522, 4-methyl-2-(3,4-dimethylphenyl)-1-(4-sulfamoylphenyl-1H-pyrrole), MK-663 (etoricoxib), NS-398, parecoxib, RS-57067, SC-58125, SD-8381, SVT-2016, S-2474, T-614, VIOXX® (rofecoxib) and the like.

EGFR inhibitors include ABX-EGF, anti-EGFR immunoliposomes, EGF-vaccine, EMD-7200, ERBITUX® (cetuximab), HR3, IgA antibodies, IRESSA® (gefitinib), TARCEVA® (erlotinib or OSI-774), TP-38, EGFR fusion protein, TYKERB® (lapatinib) and the like.

ErbB2 receptor inhibitors include CP-724-714, CI-1033 (canertinib), HERCEPTIN® (trastuzumab), TYKERB® (lapatinib), OMNITARG® (2C4, petuzumab), TAK-165, GW-572016 (ionafarnib), GW-282974, EKB-569, PI-166, dHER2 (HER2 vaccine), APC-8024 (HER-2 vaccine), anti-HER2/neu bispecific antibody, B7.her2IgG3, AS HER2 trifunctional bispecfic antibodies, mAB AR-209, mAB 2B-1 and the like.

Histone deacetylase inhibitors include depsipeptide, LAQ-824, MS-275, trapoxin, suberoylanilide hydroxamic acid (SAHA), TSA, valproic acid and the like.

HSP-90 inhibitors include 17-AAG-nab, 17-AAG, CNF-101, CNF-1010, CNF-2024, 17-DMAG, geldanamycin, IPI-504, KOS-953, MYCOGRAB® (human recombinant antibody to HSP-90), NCS-683664, PU24FCl, PU-3, radicicol, SNX-2112, STA-9090 VER49009 and the like.

Inhibitors of inhibitors of apoptosis proteins include HGS1029, GDC-0145, GDC-0152, LCL-161, LBW-242 and the like.

Antibody drug conjugates include anti-CD22-MC-MMAF, anti-CD22-MC-MMAE, anti-CD22-MCC-DM1, CR-011-vcMMAE, PSMA-ADC, MEDI-547, SGN-19Am SGN-35, SGN-75 and the like

Activators of death receptor pathway include TRAIL, antibodies or other agents that target TRAIL or death receptors (e.g., DR4 and DR5) such as Apomab, conatumumab, ETR2-STO1, GDC0145 (lexatumumab), HGS-1029, LBY-135, PRO-1762 and trastuzumab.

Kinesin inhibitors include Eg5 inhibitors such as AZD4877, ARRY-520; CENPE inhibitors such as GSK923295A and the like.

JAK-2 inhibitors include CEP-701 (lesaurtinib), XL019 and INCB018424 and the like.

MEK inhibitors include ARRY-142886, ARRY-438162 PD-325901, PD-98059 and the like.

mTOR inhibitors include AP-23573, CCI-779, everolimus, RAD-001, rapamycin, temsirolimus, ATP-competitive TORC1/TORC2 inhibitors, including PI-103, PP242, PP30, Torin 1 and the like.

Non-steroidal anti-inflammatory drugs include AMIGESIC® (salsalate), DOLOBID® (diflunisal), MOTRIN® (ibuprofen), ORUDIS® (ketoprofen), RELAFEN® (nabumetone), FELDENE® (piroxicam), ibuprofen cream, ALEVE® (naproxen) and NAPROSYN® (naproxen), VOLTAREN® (diclofenac), INDOCIN® (indomethacin), CLINORIL® (sulindac), TOLECTIN® (tolmetin), LODINE® (etodolac), TORADOL® (ketorolac), DAYPRO® (oxaprozin) and the like.

PDGFR inhibitors include C-451, CP-673, CP-868596 and the like.

Platinum chemotherapeutics include cisplatin, ELOXATIN® (oxaliplatin) eptaplatin, lobaplatin, nedaplatin, PARAPLATIN® (carboplatin), satraplatin, picoplatin and the like.

Polo-like kinase inhibitors include BI-2536 and the like.

Phosphoinositide-3 kinase (PI3K) inhibitors include wortmannin, LY294002, XL-147, CAL-120, ONC-21, AEZS-127, ETP-45658, PX-866, GDC-0941, BGT226, BEZ235, XL765 and the like.

Thrombospondin analogs include ABT-510, ABT-567, ABT-898, TSP-1 and the like.

VEGFR inhibitors include AVASTIN® (bevacizumab), ABT-869, AEE-788, ANGIOZYME™ (a ribozyme that inhibits angiogenesis (Ribozyme Pharmaceuticals (Boulder, Colo.) and Chiron, (Emeryville, Calif.)), axitinib (AG-13736), AZD-2171, CP-547,632, IM-862, MACUGEN (pegaptamib), NEXAVAR® (sorafenib, BAY43-9006), pazopanib (GW-786034), vatalanib (PTK-787, ZK-222584), SUTENT® (sunitinib, SU-11248), VEGF trap, ZACTIMA™ (vandetanib, ZD-6474) and the like.

Antibiotics include intercalating antibiotics aclarubicin, actinomycin D, amrubicin, annamycin, adriamycin, BLENOXANE® (bleomycin), daunorubicin, CAELYX® or MYOCET® (liposomal doxorubicin), elsamitrucin, epirbucin, glarbuicin, ZAVEDOS® (idarubicin), mitomycin C, nemorubicin, neocarzinostatin, peplomycin, pirarubicin, rebeccamycin, stimalamer, streptozocin, VALSTAR® (valrubicin), zinostatin and the like.

Topoisomerase inhibitors include aclarubicin, 9-aminocamptothecin, amonafide, amsacrine, becatecarin, belotecan, BN-80915, CAMPTOSAR® (irinotecan hydrochloride), camptothecin, CARDIOXANE® (dexrazoxine), diflomotecan, edotecarin, ELLENCE® or PHARMORUBICIN® (epirubicin), etoposide, exatecan, 10-hydroxycamptothecin, gimatecan, lurtotecan, mitoxantrone, orathecin, pirarbucin, pixantrone, rubitecan, sobuzoxane, SN-38, tafluposide, topotecan and the like.

Antibodies include AVASTIN® (bevacizumab), CD40-specific antibodies, chTNT-1/B, denosumab, ERBITUX® (cetuximab), HUMAX-CD4® (zanolimumab), IGF1R-specific antibodies, lintuzumab, PANOREX® (edrecolomab), RENCAREX® (WX G250), RITUXAN® (rituximab), ticilimumab, trastuzimab, CD20 antibodies types I and II and the like.

Hormonal therapies include ARIMIDEX® (anastrozole), AROMASIN® (exemestane), arzoxifene, CASODEX® (bicalutamide), CETROTIDE® (cetrorelix), degarelix, deslorelin, DESOPAN® (trilostane), dexamethasone, DROGENIL® (flutamide), EVISTA® (raloxifene), AFEMA™ (fadrozole), FARESTON® (toremifene), FASLODEX® (fulvestrant), FEMARA® (letrozole), formestane, glucocorticoids, HECTOROL® (doxercalciferol), RENAGEL® (sevelamer carbonate), lasofoxifene, leuprolide acetate, MEGACE® (megesterol), MIFEPREX® (mifepristone), NILANDRON™ (nilutamide), NOLVADEX® (tamoxifen citrate), PLENAXIS™ (abarelix), prednisone, PROPECIA® (finasteride), rilostane, SUPREFACT® (buserelin), TRELSTAR® (luteinizing hormone releasing hormone (LHRH)), VANTAS® (Histrelin implant), VETORYL® (trilostane or modrastane), ZOLADEX® (fosrelin, goserelin) and the like.

Deltoids and retinoids include seocalcitol (EB1089, CB1093), lexacalcitrol (KH1060), fenretinide, PANRETIN® (aliretinoin), ATRAGEN® (liposomal tretinoin), TARGRETIN® (bexarotene), LGD-1550 and the like.

PARP inhibitors include ABT-888 (veliparib), olaparib, KU-59436, AZD-2281, AG-014699, BSI-201, BGP-15, INO-1001, ONO-2231 and the like.

Plant alkaloids include, but are not limited to, vincristine, vinblastine, vindesine, vinorelbine and the like.

Proteasome inhibitors include VELCADE® (bortezomib), MG132, NPI-0052, PR-171 and the like.

Examples of immunologicals include interferons and other immune-enhancing agents. Interferons include interferon alpha, interferon alpha-2a, interferon alpha-2b, interferon beta, interferon gamma-1a, ACTIMMUNE® (interferon gamma-1b) or interferon gamma-n1, combinations thereof and the like. Other agents include ALFAFERONE®, (IFN-α), BAM-002 (oxidized glutathione), BEROMUN® (tasonermin), BEXXAR® (tositumomab), CAMPATH® (alemtuzumab), CTLA4 (cytotoxic lymphocyte antigen 4), decarbazine, denileukin, epratuzumab, GRANOCYTE® (lenograstim), lentinan, leukocyte alpha interferon, imiquimod, MDX-010 (anti-CTLA-4), melanoma vaccine, mitumomab, molgramostim, MYLOTARG™ (gemtuzumab ozogamicin), NEUPOGEN® (filgrastim), OncoVAC-CL, OVAREX® (oregovomab), pemtumomab (Y-muHMFG1), PROVENGE® (sipuleucel-T), sargaramostim, sizofilan, teceleukin, THERACYS® (Bacillus Calmette-Guerin), ubenimex, VIRULIZIN® (immunotherapeutic, Lorus Pharmaceuticals), Z-100 (Specific Substance of Maruyama (SSM)), WF-10 (Tetrachlorodecaoxide (TCDO)), PROLEUKIN® (aldesleukin), ZADAXIN® (thymalfasin), ZENAPAX® (daclizumab), ZEVALIN® (90Y-Ibritumomab tiuxetan) and the like.

Biological response modifiers are agents that modify defense mechanisms of living organisms or biological responses, such as survival, growth or differentiation of tissue cells to direct them to have anti-tumor activity and include krestin, lentinan, sizofiran, picibanil PF-3512676 (CpG-8954), ubenimex and the like.

Pyrimidine analogs include cytarabine (ara C or Arabinoside C), cytosine arabinoside, doxifluridine, FLUDARA® (fludarabine), 5-FU (5-fluorouracil), floxuridine, GEMZAR® (gemcitabine), TOMUDEX® (ratitrexed), TROXATYL™ (triacetyluridine troxacitabine) and the like.

Purine analogs include LANVIS® (thioguanine) and PURI-NETHOL® (mercaptopurine).

Antimitotic agents include batabulin, epothilone D (KOS-862), N-(2-((4-hydroxyphenyl)amino)pyridin-3-yl)-4-methoxybenzenesulfonamide, ixabepilone (BMS 247550), paclitaxel, TAXOTERE® (docetaxel), PNU100940 (109881), patupilone, XRP-9881 (larotaxel), vinflunine, ZK-EPO (synthetic epothilone) and the like.

Ubiquitin ligase inhibitors include MDM2 inhibitors, such as nutlins, NEDD8 inhibitors such as MLN4924 and the like.

Compounds of this invention can also be used as radiosensitizers that enhance the efficacy of radiotherapy. Examples of radiotherapy include external beam radiotherapy, teletherapy, brachytherapy and sealed, unsealed source radiotherapy and the like.

Additionally, compounds having Formula (I) may be combined with other chemotherapeutic agents such as ABRAXANE™ (ABI-007), ABT-100 (farnesyl transferase inhibitor), ADVEXIN® (Ad5CMV-p53 vaccine), ALTOCOR® or MEVACOR® (lovastatin), AMPLIGEN® (poly I:poly C12U, a synthetic RNA), APTOSYN® (exisulind), AREDIA® (pamidronic acid), arglabin, L-asparaginase, atamestane (1-methyl-3,17-dione-androsta-1,4-diene), AVAGE® (tazarotene), AVE-8062 (combreastatin derivative) BEC2 (mitumomab), cachectin or cachexin (tumor necrosis factor), canvaxin (vaccine), CEAVAC® (cancer vaccine), CELEUK® (celmoleukin), CEPLENE® (histamine dihydrochloride), CERVARIX® (human papillomavirus vaccine), CHOP® (C: CYTOXAN® (cyclophosphamide); H: ADRIAMYCIN® (hydroxydoxorubicin); 0: Vincristine (ONCOVIN®); P: prednisone), CYPAT™ (cyproterone acetate), combrestatin A4P, DAB(389)EGF (catalytic and translocation domains of diphtheria toxin fused via a His-Ala linker to human epidermal growth factor) or TransMID-107R™ (diphtheria toxins), dacarbazine, dactinomycin, 5,6-dimethylxanthenone-4-acetic acid (DMXAA), eniluracil, EVIZON™ (squalamine lactate), DIMERICINE® (T4N5 liposome lotion), discodermolide, DX-8951f (exatecan mesylate), enzastaurin, EP0906 (epithilone B), GARDASIL® (quadrivalent human papillomavirus (Types 6, 11, 16, 18) recombinant vaccine), GASTRIMMUNE®, GENASENSE®, GMK (ganglioside conjugate vaccine), GVAX® (prostate cancer vaccine), halofuginone, histerelin, hydroxycarbamide, ibandronic acid, IGN-101, IL-13-PE38, IL-13-PE38QQR (cintredekin besudotox), IL-13-pseudomonas exotoxin, interferon-α, interferon-γ, JUNOVAN™ or MEPACT™ (mifamurtide), lonafarnib, 5,10-methylenetetrahydrofolate, miltefosine (hexadecylphosphocholine), NEOVASTAT®(AE-941), NEUTREXIN® (trimetrexate glucuronate), NIPENT® (pentostatin), ONCONASE® (a ribonuclease enzyme), ONCOPHAGE® (melanoma vaccine treatment), ONCOVAX® (IL-2 Vaccine), ORATHECIN™ (rubitecan), OSIDEM® (antibody-based cell drug), OVAREX® MAb (murine monoclonal antibody), paclitaxel, PANDIMEX™ (aglycone saponins from ginseng comprising 20(S)protopanaxadiol (aPPD) and 20(S)protopanaxatriol (aPPT)), panitumumab, PANVAC®-VF (investigational cancer vaccine), pegaspargase, PEG Interferon A, phenoxodiol, procarbazine, rebimastat, REMOVAB® (catumaxomab), REVLIMID® (lenalidomide), RSR13 (efaproxiral), SOMATULINE® LA (lanreotide), SORIATANE® (acitretin), staurosporine (Streptomyces staurospores), talabostat (PT100), TARGRETIN® (bexarotene), TAXOPREXIN® (DHA-paclitaxel), TELCYTA® (canfosfamide, TLK286), temilifene, TEMODAR® (temozolomide), tesmilifene, thalidomide, THERATOPE® (STn-KLH), thymitaq (2-amino-3,4-dihydro-6-methyl-4-oxo-5-(4-pyridylthio)quinazoline dihydrochloride), TNFERADE™ (adenovector: DNA carrier containing the gene for tumor necrosis factor-α), TRACLEER® or ZAVESCA® (bosentan), tretinoin (Retin-A), tetrandrine, TRISENOX® (arsenic trioxide), VIRULIZIN®, ukrain (derivative of alkaloids from the greater celandine plant), vitaxin (anti-alphavbeta3 antibody), XCYTRIN® (motexafin gadolinium), XINLAY™ (atrasentan), XYOTAX™ (paclitaxel poliglumex), YONDELIS® (trabectedin), ZD-6126, ZINECARD® (dexrazoxane), ZOMETA® (zolendronic acid), zorubicin and the like.

Data

Determination of the utility of compounds having Formula (I) as binders to and inhibitors of NAMPT was performed using Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) binding assays.

Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Binding Assay of NAMPT

Test compounds were serially diluted (typically 11 half log dilutions) in neat DMSO to 50× final concentrations prior to dilution with assay buffer (50 mM HEPES (NaOH), pH 7.5, 100 mM NaCl, 10 mM MgCl₂, 1 mM DTT, 1% Glycerol) to 3× and 6% DMSO. Six μL were transferred to 384-well low-volume plates (Owens Corning #3673). To this, 12 μL of a 1.5× solution containing enzyme, probe and antibody were added. Final concentrations in the 18 μl, reactions were 1× assay buffer, 2% DMSO, 6.8 nM NAMPT (human, recombinant, C-terminally His-tagged), 200 nM probe (a potent nicotinamide-competitive inhibitor conjugated to Oregon Green 488) and 1 nM Tb-anti-His antibody (Invitrogen # PV5895). Reactions were equilibrated at room temperature for 3 hours prior to reading on an Envision multi-label plate reader (Perkin Elmer; Ex=337 nm, Em=520 and 495 nm). Time-resolved FRET ratios (Em₅₂₀/Em₄₉₅) were normalized to controls, plotted as a function of compound concentration and fit with the four-parameter logistic equation to determine IC50s.

Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Binding Assay of NAMPT with PRPP

Compound handling and data processing were identical to the assay in the absence of substrates (above). Final concentrations were 1× assay buffer, 2% DMSO, 2 nM NAMPT, 2 nM probe, 1 nM Tb-anti-His antibody (Invitrogen # PV5895), 200 μM PRPP and 2.5 mM ATP. Reactions were equilibrated for 16 hours prior to measurement to allow for potential enzymatic modification of test compounds.

Table 1 shows the utility of compounds having Formula I to functionally inhibit NAMPT.

TABLE 1 TR-FRET TR-FRET Binding- Binding- IC50 (with Example IC50 (μM) PRPP) (μM) 1 0.120000 0.000386 2 0.022300 0.020000 3 0.357000 0.019200 4 0.424000 0.024000 5 0.107000 0.010200 6 0.544000 0.002340 7 0.104000 0.084700 8 3.360000 0.005300 9 8.620000 0.017200 10 0.034500 0.000518 11 2.370000 0.001930 12 1.410000 0.002050 13 0.858000 0.002880 14 3.840000 0.003080 15 1.660000 0.002490 16 2.480000 0.004130 17 3.510000 0.002360 18 2.740000 0.005320 19 1.170000 0.000554 20 0.006740 0.000296 21 7.380000 0.000507 22 0.011700 0.000169 23 1.950000 0.000610 24 5.880000 0.000861 25 0.028100 0.000598 26 0.005050 0.000761 27 nd 0.011200 28 nd 0.002510 29 0.079800 0.016700 30 0.015000 0.000267 31 0.135000 0.000693 32 0.010200 0.000284 33 0.109000 0.000342 34 0.071400 0.000886 35 0.091600 0.000866 36 0.040100 0.000882 37 0.068900 0.000983 38 0.046500 0.000900 39 0.104000 0.001050 40 0.042800 0.000490 41 0.069200 0.000780 42 0.226000 0.002390 43 0.086500 0.000803 44 0.138000 0.001010 45 0.087300 0.001080 46 0.093400 0.001020 47 0.080500 0.001780 48 0.112000 0.000861 49 0.066100 0.001020 50 0.063500 0.001100 51 0.109000 0.001170 52 0.051000 0.000696 53 0.025600 0.000689 54 0.072100 0.000806 55 0.168000 0.002220 56 0.360000 0.000812 57 0.180000 0.001070 58 0.059500 0.000683 59 0.027900 0.000606 60 0.150000 0.001010 61 0.033700 0.000675 62 0.041600 0.000666 63 0.052700 0.000514 64 0.055200 0.000927 65 0.121000 0.000704 66 0.056600 0.000535 67 0.452000 0.000497 68 0.080600 0.000569 69 0.068600 0.000918 70 0.035700 0.000742 71 0.041200 0.014600 72 0.006540 0.007340 73 0.224000 0.071100 74 0.911000 0.000666 75 1.340000 0.000719 76 1.920000 0.000440 77 3.010000 0.000832 78 0.265000 0.000632 79 2.690000 0.000824 80 1.600000 0.000686 81 3.720000 0.001130 82 0.955000 0.000526 83 1.210000 0.000503 84 6.070000 0.001810 85 0.032200 0.017000 86 1.260000 0.000833 87 1.390000 0.001270 88 0.574000 0.000640 89 2.000000 0.000647 90 1.410000 0.000902 91 0.992000 0.000868 92 0.784000 0.000548 93 1.220000 0.001250 94 2.270000 0.001030 95 1.360000 0.001020 96 0.115000 0.282000 97 0.036600 0.131000 98 0.013000 0.000209 99 0.013500 0.000169 100 0.030600 0.000497 101 0.016500 0.000486 102 0.008840 0.000210 103 0.056200 0.000493 104 0.001200 0.000193 105 0.296000 0.000244 106 0.160000 0.000221 107 0.163000 0.000169 108 0.003330 0.000176 109 0.005030 0.000398 110 0.006630 0.000169 111 0.002840 0.000199 112 0.040200 0.000362 113 0.060600 0.000254 114 0.083900 0.000247 115 0.048200 0.000178 116 0.026500 0.000204 117 0.006270 0.000355 118 0.014100 0.000169 119 0.006120 0.000169 120 0.011600 0.000294 121 0.009940 0.000169 122 0.007940 0.000169 123 0.065600 0.000282 124 0.123000 0.000278 125 0.015400 0.000518 126 0.014900 0.000359 127 0.003640 0.000391 128 0.008360 0.000610 129 0.004490 0.000367 130 0.288000 0.000535 131 0.069900 0.000474 132 0.008460 0.000441 133 0.012000 0.000626 134 0.016900 0.000361 135 0.033900 0.000293 136 0.020400 0.000635 137 0.017600 0.000459 138 0.021800 0.000445 139 0.012000 0.000473 140 0.011000 0.008870 141 1.240000 0.075200 142 1.560000 0.032800 143 0.017000 0.031100 144 0.014600 0.034400 145 0.040600 0.058100 146 0.065900 0.109000 147 0.034600 0.001470 148 0.042900 0.020100 149 0.020700 0.054300 150 0.006530 0.043800 151 0.017400 0.043600 152 0.087600 0.101000 153 0.266000 0.122000 154 0.524000 0.016100 155 0.294000 0.044000 156 0.396000 0.084300 157 1.070000 0.192000 158 2.900000 0.224000 159 0.137000 0.061200 160 0.074500 0.070800 161 0.128000 0.059700 162 0.144000 0.071000 163 0.166000 0.083100 164 0.987000 0.124000 165 0.035200 0.068300 166 2.270000 0.206000 167 3.740000 0.204000 168 2.940000 0.171000 169 0.033700 0.067900 170 0.091500 0.089800 171 0.019700 0.037900 172 0.286000 0.170000 173 0.524000 0.154000 174 2.100000 0.158000 175 0.664000 0.161000 176 0.165000 0.111000 177 0.060400 0.091300 178 0.247000 0.065200 179 0.099200 0.070700 180 0.304000 0.123000 181 0.284000 0.128000 182 0.140000 0.104000 183 1.040000 0.185000 184 0.625000 0.078900 185 0.081300 0.044100 186 0.098900 0.118000 187 0.010200 0.027300 188 0.020500 0.049900 189 0.006910 0.026900 190 1.910000 0.103000 191 0.743000 0.184000 192 0.047300 0.072300 193 0.040200 0.054000 194 0.122000 0.062600 195 0.305000 0.094100 196 0.083800 0.098500 197 0.126000 0.079800 198 0.084500 0.103000 199 0.033700 0.028000 200 0.033100 0.034400 201 0.012100 0.018200 202 0.117000 0.089500 203 0.034200 0.021100 204 0.380000 0.002760 205 0.025100 0.034000 206 0.023800 0.024100 207 0.141000 0.086700 208 0.117000 0.049600 209 0.061700 0.028900 210 0.031700 0.038300 211 0.031900 0.000801 212 0.070400 0.000787 213 0.104000 0.000678 214 0.165000 0.000841 215 0.068200 0.001140 216 0.228000 0.001410 217 0.043900 0.001510 218 0.265000 0.001640 219 0.105000 0.000480 220 0.267000 0.001010 221 0.164000 0.000576 222 0.215000 0.001030 223 0.150000 0.000959 224 0.151000 0.001390 225 0.158000 0.001070 226 0.242000 0.000896 227 0.065900 0.000696 228 0.054600 0.000911 229 0.048000 0.000584 230 0.158000 0.000843 231 0.174000 0.000831 232 0.141000 0.000563 233 0.113000 0.000614 234 0.185000 0.000730 235 0.283000 0.001410 236 0.130000 0.001110 237 0.240000 0.001270 238 0.207000 0.000554 239 0.112000 0.000833 240 0.192000 0.000925 241 0.131000 0.000811 242 0.278000 0.001170 243 0.269000 0.000970 244 0.449000 0.000916 245 0.101000 0.000707 246 0.178000 0.000676 247 0.086000 0.001020 248 0.082600 0.000817 249 0.059900 0.000600 250 0.107000 0.000641 251 0.230000 0.000880 252 0.238000 0.001100 253 0.134000 0.000639 254 0.033900 0.011200 255 0.047300 0.037800 256 0.091100 0.038400 257 0.064700 0.041900 258 0.108000 0.034800 259 0.032500 0.017700 260 0.075400 0.019000 261 0.062900 0.023700 262 0.130000 0.034300 263 0.031300 0.020200 264 0.052800 0.013400 265 0.029500 0.021800 266 0.120000 0.053200 267 0.274000 0.056500 268 0.119000 0.042100 269 0.037700 0.022300 270 0.074800 0.035700 271 0.078000 0.025200 272 0.165000 0.052400 273 0.128000 0.042100 274 0.152000 0.064500 275 0.231000 0.045100 276 0.134000 0.034900 277 0.062400 0.026700 278 0.075800 0.033400 279 0.020200 0.015500 280 0.123000 0.051900 281 0.020500 0.014900 282 0.383000 0.090000 283 0.072300 0.032200 284 0.062400 0.038200 285 0.149000 0.086200 286 0.127000 0.066400 287 0.125000 0.063200 288 0.044900 0.019500 289 0.041600 0.032100 290 0.099300 0.045700 291 0.045600 0.018200 292 0.099000 0.064700 293 0.078200 0.025300 294 0.112000 0.055100 295 0.077600 0.051000 296 0.149000 0.057100 297 0.104000 0.047000 298 0.192000 0.061100 299 0.154000 0.086900 300 0.064200 0.039100 301 0.143000 0.048300 302 0.150000 0.048300 303 0.030900 0.015500 304 0.055400 0.024200 305 0.109000 0.035000 306 0.112000 0.046300 307 0.037700 0.015900 308 0.036900 0.018400 309 4.150000 0.000293 310 0.456000 0.005370 311 0.030200 0.003960 312 1.130000 0.008940 313 0.217000 0.004130 314 3.860000 0.000572 315 0.469000 0.000641 316 0.104000 0.000924 317 0.043900 0.000991 318 0.037700 0.000716 319 0.024900 0.000747 320 0.026400 0.000611 321 0.038700 0.000864 322 0.028600 0.000843 323 0.025300 0.000885 324 0.047300 0.001040 325 0.014000 0.001080 326 0.018300 0.000626 327 0.012600 0.000655 328 0.012200 0.000614 329 0.024200 0.000616 330 0.031700 0.000887 331 0.024900 0.000830 332 0.021900 0.000699 333 0.050900 0.000631 334 0.018200 0.000578 335 0.210000 0.001020 336 0.077300 0.000494 337 0.050000 0.000522 338 0.027600 0.000520 339 0.017900 0.000663 340 0.017600 0.000722 341 0.035100 0.000727 342 0.013100 0.000698 343 0.006180 0.000728 344 0.037800 0.000569 345 0.009540 0.000392 346 0.030800 0.000457 347 0.066200 0.000940 348 0.015300 0.000628 349 0.059500 0.000738 350 0.004620 0.000642 351 0.037100 0.000765 352 0.095800 0.000615 353 0.088200 0.000472 354 0.082800 0.000837 355 0.115000 0.000986 356 0.067700 0.000878 357 0.017700 0.001140 358 0.015900 0.000815 359 0.021300 0.000869 360 0.022000 0.000782 361 0.037400 0.000988 362 0.015200 0.000832 363 0.010400 0.000798 364 0.036900 0.000334 365 0.050100 0.001050 366 0.035100 0.000681 367 0.033700 0.000735 368 0.064000 0.000635 369 0.018300 0.000479 370 0.030535 0.000555 371 0.056700 0.000438 372 0.016600 0.000633 373 0.022400 0.000576 374 0.023900 0.000973 375 0.006720 0.000679 376 0.003220 0.000468 377 0.016200 0.000632 378 0.077100 0.000632 379 0.015900 0.000432 380 0.109000 0.000883 381 0.015100 0.001130 382 0.065800 0.000657 383 0.103000 0.000859 384 0.028800 0.000497 385 0.055100 0.001240 528 0.026200 0.017300 nd = no data

NAMPT Cell Proliferation Assay

PC3 cells were seeded in 96-well black plates (Corning #3904) at 500 cell/swell in 90 μl of RPMI media containing 10% heat-inactivated FBS and incubated overnight at 37° C. and 5% CO₂ to allow cells to attach to wells. The following day, test compounds were serially diluted in neat DMSO to 1000× final concentrations prior to dilution with RPMI media to 10× and 1% DMSO. Ten μL of the 10× compounds were then transferred to wells containing cells to produce a dose response of 10-fold dilutions from 10 μM to 1×10⁻⁵ μM. Cells were incubated for 5 days at 37° C. and 5% CO₂, then cell viability was measured using Cell Titer Glo reagent (Promega #G7571). Percent inhibition values were calculated and fitted to a sigmoidal dose response curves using Assay Explorer software to determine IC50s. To assess whether inhibition of cell viability was due to NAMPT inhibition, the proliferation assay was also performed in the presence of 0.3 mM nicotinamide mononucleotide.

Table 2 shows the results of the cell proliferation assay.

TABLE 2 Cell Titer- Glo- IC50 Example (μM) 1 0.00656 2 >10 3 7.33 4 0.112 5 0.00675 6 0.0677 7 0.876 8 0.0708 9 0.739 10 0.00184 11 0.0227 12 0.0844 13 0.0791 14 0.0548 15 0.0347 16 0.0926 17 0.0937 18 0.148 19 0.0564 20 0.00028 21 0.15 22 0.00125 23 0.0725 24 0.169 25 0.00141 26 0.000682 27 >10 28 >10 29 0.135 30 0.00197 31 0.0069 32 0.00654 33 0.00366 34 0.0068 35 0.00692 36 0.00966 37 0.00648 38 0.00639 39 0.00738 40 0.00217 41 0.00376 42 0.0646 43 0.00688 44 0.00547 45 0.00677 46 0.00301 47 0.00335 48 0.00288 49 0.00696 50 0.00895 51 0.00362 52 0.00628 53 0.00367 54 0.00331 55 0.0211 56 0.00927 57 0.00875 58 0.00648 59 0.00614 60 0.00507 61 0.00352 62 0.0142 63 0.00635 64 0.00632 65 0.00638 66 0.00581 67 0.386 68 0.00354 69 0.00422 70 0.00397 71 0.0729 72 0.00569 73 1.98 74 0.0114 75 nd 76 0.0191 77 nd 78 0.0212 79 nd 80 0.0255 81 nd 82 0.00955 83 nd 84 0.0389 85 0.0205 86 0.0697 87 0.0317 88 0.0663 89 0.0646 90 0.0601 91 0.0599 92 0.024 93 0.0584 94 0.0657 95 0.0739 96 7.61 97 0.922 98 0.00605 99 0.00572 100 0.00613 101 0.00031 102 0.00059 103 0.00144 104 0.00018 105 0.00617 106 0.0618 107 0.00688 108 0.00013 109 0.00066 110 0.00026 111 0.00064 112 0.00076 113 0.00634 114 0.0181 115 0.0004 116 0.00064 117 0.00063 118 0.00022 119 0.00019 120 0.00023 121 0.00062 122 0.00061 123 0.00103 124 0.00144 125 0.00024 126 0.00026 127 0.00014 128 0.00016 129 0.00016 130 0.00181 131 0.0003 132 0.00023 133 0.00062 134 0.00064 135 0.0003 136 0.00023 137 0.00031 138 0.00023 139 0.00018 140 0.00354 141 0.834 142 0.7406 143 0.00496 144 0.0184 145 0.0709 146 0.0707 147 0.00095 148 0.0761 149 0.058 150 0.0589 151 0.0609 152 0.116 153 0.699 154 0.803 155 0.701 156 0.712 157 0.948 158 1.3 159 0.182 160 0.173 161 0.213 162 0.225 163 0.12 164 0.202 165 0.0682 166 1.07 167 6.25 168 1.01 169 0.0654 170 0.0655 171 0.0681 172 0.329 173 0.627 174 1.13 175 0.683 176 0.218 177 0.107 178 0.3 179 0.192 180 0.164 181 0.238 182 0.0879 183 0.346 184 0.604 185 0.0742 186 0.627 187 0.0206 188 0.0224 189 0.0146 190 0.694 191 0.677 192 0.0693 193 0.071 194 0.124 195 0.701 196 0.111 197 0.103 198 0.0716 199 0.0974 200 0.0719 201 0.0609 202 0.168 203 0.606 204 0.0245 205 0.0387 206 0.0674 207 0.671 208 0.593 209 0.0816 210 0.0627 211 0.00594 212 0.00579 213 0.00688 214 0.00909 215 0.00695 216 0.00599 217 0.00255 218 0.00886 219 0.00886 220 0.0132 221 0.00899 222 0.0155 223 0.0055 224 0.00752 225 0.00876 226 0.00889 227 0.00453 228 0.00597 229 0.00646 230 0.00905 231 0.00875 232 0.00874 233 0.00873 234 0.0105 235 0.0124 236 0.00925 237 0.0103 238 0.0157 239 0.0067 240 0.0103 241 0.00773 242 0.00906 243 0.00928 244 0.0104 245 0.00706 246 0.00965 247 0.00798 248 0.00658 249 0.00235 250 0.00911 251 0.00787 252 0.00951 253 0.00809 254 0.012 255 0.0241 256 0.145 257 0.0761 258 0.309 259 0.0726 260 0.0746 261 0.0715 262 0.119 263 0.0595 264 0.1 265 0.0701 266 0.083 267 0.622 268 0.0829 269 0.0604 270 0.0627 271 0.0515 272 0.0795 273 0.634 274 0.107 275 0.683 276 0.13 277 0.0731 278 0.0791 279 0.00972 280 0.0719 281 0.0169 282 0.629 283 0.0725 284 0.0666 285 0.0692 286 0.074 287 0.121 288 0.0248 289 0.0532 290 0.0807 291 0.0736 292 0.0934 293 0.0723 294 0.0832 295 0.0715 296 0.0689 297 0.0932 298 0.0979 299 0.0846 300 0.0259 301 0.0905 302 0.0824 303 0.0586 304 0.0332 305 0.102 306 0.0347 307 0.0208 308 0.0614 309 8.2 310 0.0161 311 0.0029 312 0.0217 313 0.00603 314 0.621 315 0.0868 316 0.00312 317 0.00183 318 0.00272 319 0.00124 320 0.00237 321 0.00321 322 0.00214 323 0.00281 324 0.00708 325 0.00128 326 0.00577 327 0.00123 328 0.00159 329 0.00283 330 0.00138 331 0.00209 332 0.00099 333 0.00568 334 0.00097 335 0.00607 336 0.00826 337 0.00694 338 0.00111 339 0.00183 340 0.00242 341 0.00198 342 0.0023 343 0.00653 344 0.0089 345 0.00199 346 0.0038 347 0.00806 348 0.002 349 0.00728 350 0.00075 351 0.00236 352 0.00888 353 0.00715 354 0.00751 355 0.00979 356 0.00909 357 0.00147 358 0.00186 359 0.00177 360 0.00235 361 0.00277 362 0.00261 363 0.0056 364 0.00863 365 0.00784 366 0.00657 367 0.00638 368 0.0077 369 0.00214 370 0.00879 371 0.00894 372 0.00706 373 0.00595 374 0.00632 375 0.00087 376 0.00062 377 0.00213 378 0.00709 379 0.00107 380 0.00757 381 0.00187 382 0.00899 383 0.0627 384 0.00827 385 0.0232 386 0.00318 387 0.0022 388 0.00088 389 0.00717 390 0.0015 391 0.00599 392 0.00354 393 0.00372 394 0.00199 395 0.00214 396 0.06848 397 0.00335 398 0.00819 399 0.00635 400 0.0068 401 0.00854 402 0.00168 403 0.0041 404 0.0027 405 0.00675 406 0.00742 407 0.00101 408 0.0299 409 0.00672 410 0.00868 411 0.00715 412 0.00137 413 0.01 414 0.0074 415 0.00228 416 0.00112 417 0.00645 418 0.00826 419 0.00217 420 0.00235 421 0.00372 422 0.00112 423 0.00038 424 0.0015 425 0.00091 426 0.00207 427 0.00203 428 0.00019 429 0.0008 430 0.00142 431 0.00167 432 0.008 433 0.00577 434 0.00635 435 0.0003 436 0.00067 437 0.00098 438 0.00196 439 0.00336 440 0.0018 441 0.00683 442 0.00625 443 0.00565 444 0.078 445 0.0191 446 0.108 447 0.903 448 0.00932 449 0.678 450 0.0509 451 0.0868 452 0.0632 453 0.105 454 0.106 455 0.458 456 0.0395 457 0.142 458 0.0644 459 0.0369 460 0.223 461 0.646 462 0.214 463 0.0709 464 0.0659 465 0.616 466 0.00807 467 0.0156 468 0.73 469 0.00861 470 0.715 471 0.072 472 0.00656 473 0.0093 474 0.0685 475 0.594 476 0.0174 477 0.235 478 0.0143 479 0.0689 480 0.00424 481 0.0121 482 0.0326 483 0.00214 484 0.00056 485 0.00635 486 0.00624 487 0.072 488 0.0642 489 0.00207 490 0.00068 491 0.00845 492 0.00373 493 0.00673 494 0.00105 495 0.00706 496 0.0063 497 0.0234 498 0.00664 499 0.0121 500 0.00102 501 0.00607 502 0.00474 503 0.0582 504 0.00775 505 0.00684 506 0.00128 507 0.00834 508 0.00079 509 0.00119 510 0.0664 511 0.00082 512 0.0155 513 0.0035 514 0.00032 515 0.00085 516 0.00226 517 0.00921 518 0.00087 519 0.00321 520 0.00047 521 0.00472 522 0.00078 523 0.00099 524 0.00573 525 0.00093 526 0.00094 527 0.00778 528 0.01923 529 0.00933 530 0.00202 531 0.0176 532 0.00724 533 0.0246 534 0.00546 535 0.00939 536 0.00614 537 0.0033 538 0.0137 539 0.00257 540 0.00391 541 0.0042 542 0.0676 543 0.0077 544 0.00717 545 0.0152 546 0.00141 547 0.00302 548 0.0649 549 0.00067 550 0.00821 551 0.00048 552 0.00332 553 0.0441 554 0.00263 555 0.0239 556 0.00598 557 0.0102 558 0.00066 559 0.00133 560 0.00585 561 0.0622 562 0.00945 563 0.0242 564 0.0792 565 0.0741 566 0.0822 567 0.0765 568 0.0482 569 0.207 570 0.631 571 0.118 572 0.0598 573 0.0819 574 0.0553 575 0.269 576 0.0848 577 0.093 578 0.0887 579 0.267 580 0.078 581 0.0807 582 0.627 583 0.0874 584 0.0872 585 0.283 586 0.107 587 0.0814 588 0.113 589 0.0979 590 0.0822 591 0.0936 592 0.62 593 0.0634 594 0.0478 595 0.0806 596 0.0846 597 0.117 598 0.208 599 0.0797 600 0.219 601 0.0968 602 0.002 603 0.576 604 8.26127 605 1.4 606 0.0867 607 7.65 608 0.712 609 0.00205 610 0.0079 611 0.09 612 0.0536 613 0.70691 614 7.66 615 6.15 616 7.29 617 1.87 618 >10 619 >10 620 2.83 621 >10 622 >10 623 6.17 624 >10 625 1.9 626 5.22 627 0.853 628 >10 629 5.01 630 0.00812 631 0.00958 632 0.00881 633 0.00895 634 0.00922 635 0.0416 636 0.0828 637 0.00124 638 0.0299 639 0.00816 640 0.00292 641 0.0726 642 0.00726 643 0.00846 644 0.00823 645 0.0033 646 0.0587 647 0.00573 648 0.0268 649 0.00111 650 0.0869 651 0.0276 652 0.00614 653 0.00972 654 0.00276 655 0.000475 656 0.061 657 0.00844 658 0.0144 659 0.0112 660 0.00523 661 0.0216 662 0.0159 663 0.0316 664 1.15 665 7.62 666 0.008059 667 0.01248 668 >10 669 0.00188 670 0.00853 671 0.00853 672 0.00405 673 0.0116 674 0.0057 675 0.0693 676 0.00202 677 0.0093 678 0.00609 679 0.0006 680 0.00355 681 0.00902 682 0.00273 683 0.00902 684 0.0766 685 0.00828 686 0.0649 687 0.00611 688 0.0094 689 0.00968 690 0.00314 691 0.03 692 0.00423 693 0.0136 694 0.0716 695 0.00616 696 0.00467 697 0.00596 698 0.0679 699 0.065 700 0.00876 701 0.0752 702 0.00207 703 0.00843 704 0.0053 705 0.0202 706 0.0077 707 0.00693 708 0.0142 709 0.0145 710 0.0103 711 0.0595 712 0.00679 713 0.00999 714 0.0176 715 0.0118 716 0.0692 717 0.0121 718 0.00627 719 0.00963 720 0.00857 721 0.00839 722 0.0848 723 0.003507 724 0.0809 725 0.00401 726 0.0327 727 0.0046 728 0.00697 729 0.0135 730 0.00681 731 0.00050 732 0.0299 733 0.0375 734 0.00833 735 0.0689 736 0.00809 737 1.86 738 0.853926 739 7.31 740 0.914369 741 0.181262 742 0.734 743 6.62 744 2.72 745 >10 746 >10 747 5.92 748 0.00258 749 >10 750 0.226 751 0.00271 752 2.45 753 0.00892 754 0.0948 755 0.19 756 0.00908 757 0.0677 758 0.857 759 0.0062 760 0.253 761 0.0923 762 0.709 763 0.00841 764 0.022126 765 1.02 766 0.787 767 1.28 768 0.111 769 0.0186 770 0.138 771 0.0699 772 0.0636 773 0.0857 774 0.00252 775 0.00215 776 0.00764 777 0.0192 778 0.0197 779 0.00148 780 0.00407 781 0.01 782 0.0669 783 0.00646 784 0.016 785 0.00117 786 0.012 787 0.0639 788 0.00759 789 0.0284 790 0.0746 791 0.00748 792 0.0088 793 0.329 794 0.196 795 0.773 796 0.0117 797 0.0126 798 0.0664 799 0.0255 800 0.06 801 0.024555 802 0.0263 803 0.00161 804 0.00792 805 0.065 806 0.00313 807 0.00415 808 0.0411 809 0.0024 810 0.0611 811 0.011 812 0.0102 813 0.0786 814 0.0819 815 0.185 816 0.188 817 0.0641 818 0.0294 819 0.00856 820 0.0754 821 0.165 822 0.0605 823 0.247 824 0.0706 825 0.0623 826 0.0983 827 0.0737 828 0.000826 829 0.00295 830 0.00796 831 0.00725 832 0.0167 833 0.00667 834 0.0144 835 0.00235 836 0.658 837 0.769 838 1.77 839 2 840 0.0028 841 0.00355 842 0.000665 843 0.00061 844 0.00252 845 0.00209 846 0.00724 847 0.115 848 0.609 849 0.685 850 0.0705 851 0.00275 852 0.0124 853 >10 854 >10 855 0.747 856 0.729 857 0.00252 858 0.00436 859 0.0027 860 0.01 861 0.00758 862 0.00849 863 0.00567 864 0.00529 865 0.00406 866 0.00792 867 0.00784 868 0.00229 869 0.00198 870 0.0032 871 0.00361 872 0.0236 873 0.675 874 0.0711 875 >10 876 0.0292 877 0.02960 878 0.0706 879 0.00583 880 0.01540 881 0.00818 882 0.00643 883 0.0309 884 0.00275 885 0.00163 886 0.00766 887 0.00847 888 0.00976 889 0.00285 890 0.00409 891 0.0656 892 0.146 893 0.681 894 0.752 895 0.00215 896 0.00109 897 0.00156 898 .000851 899 .000401 900 0.00224 901 0.00207 902 0.00645 903 .000618 904 0.00195 905 0.0133 906 .000879 907 6.75 908 0.0925 909 0.067 910 0.00651 911 >10 912 0.0642 913 0.0663 914 0.0027 915 0.139 916 0.646 917 0.101 918 0.717 919 0.0519 920 0.00543 921 0.0029 922 0.00338 923 0.0694 924 0.00117 925 0.0101 926 0.602 927 0.0039 928 0.00256 929 0.0271 930 0.0027 2931 0.00317 932 0.00582 933 0.00239 934 0.00245 935 0.002 936 0.00218 937 0.00262 938 0.00875 939 0.00296 940 0.00197 941 0.0021 942 0.00276 943 0.0076 944 0.00714 945 0.00451 946 0.00289 947 0.00256 948 0.00226 949 0.00595 950 0.00606 951 0.00277 952 0.00217 953 0.00334 954 0.00638 955 0.00597 956 0.00640 957 0.00193 958 0.00263 959 0.00233 960 0.00286 961 0.00557 962 0.0024 963 0.00214 964 0.00184 965 0.00260 966 0.00323 967 0.00305 968 0.0037 969 .000347 970 0.0285 971 0.0708 972 0.667 973 0.00553 974 0.00784 975 0.098 976 0.0612 977 0.0124 978 1.07 979 0.072 980 0.0822 981 1.06 982 0.0835 983 0.604 984 0.696 985 0.635 986 7.47 987 0.609 988 1.24 989 0.602 990 6.81 991 0.76 992 1.51 993 0.809 994 0.059 995 0.245 996 0.104 997 0.0935 998 1.28 999 0.25 1000 0.077 1001 0.0532 1002 0.911 1003 1.07 1004 7.92 1005 0.592 1006 0.00536 1007 0.0567 1008 0.299 1009 0.0818 1010 0.0709 1011 0.113 1012 0.782 1013 0.213 1014 0.219 1015 0.0901 1016 0.212 1017 0.752 1018 0.716 1019 2.46 1020 7.27 1021 0.0477 1022 8.16 1023 0.508 1024 nd 1025 nd nd = no data

Compounds which inhibit NAMPT are useful for treating diseases in which activation of NF-KB is implicated. Such methods are useful in the treatment of a variety of diseases including inflammatory and tissue repair disorders; particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, particularly wherein the cancer is selected from breast, prostate, lung, colon, cervix, ovary, skin, CNS, bladder, pancreas, leukaemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia.

Involvement of NAMPT in the treatment of cancer is described in WO 97/48696. Involvement of NAMPT in immuno-supression is described in WO 97/48397. Involvement of NAMPT for the treatment of diseases involving angiogenesis is described in WO 2003/80054. Involvement of NAMPT for the treatment of rheumatoid arthritis and septic shock is described in WO 2008/025857. Involvement of NAMPT for the prophlaxis and treatment of ischaemia is described in WO 2009/109610.

Cancers include, but are not limited to, hematologic and solid tumor types such as acoustic neuroma, acute leukemia, acute lymphoblastic leukemia, acute myelogenous leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute t-cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer (including estrogen-receptor positive breast cancer), bronchogenic carcinoma, Burkitt's lymphoma, cervical cancer, chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocytic) leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, dysproliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing's tumor, fibrosarcoma, gastric carcinoma, germ cell testicular cancer, gestational trophobalstic disease, glioblastoma, head and neck cancer, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, liposarcoma, lung cancer (including small cell lung cancer and non-small cell lung cancer), lymphangioendothelio-sarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (lymphoma, including diffuse large B-cell lymphoma, follicular lymphoma, Hodgkin's lymphoma and non-Hodgkin's lymphoma), malignancies and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoid malignancies of T-cell or B-cell origin, leukemia, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma, peripheral T-cell lymphoma, pinealoma, polycythemia vera, prostate cancer (including hormone-insensitive (refractory) prostate cancer), rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung carcinoma, solid tumors (carcinomas and sarcomas), stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, testicular cancer (including germ cell testicular cancer), thyroid cancer, Waldenström's macroglobulinemia, testicular tumors, uterine cancer, Wilms' tumor and the like.

Schemes and Experimentals

The following abbreviations have the meanings indicated. ADDP means 1,1′-(azodicarbonyl)dipiperidine; AD-mix-β means a mixture of (DHQD)₂PHAL, K₃Fe(CN)₆, K₂CO₃, and K₂SO₄; 9-BBN means 9-borabicyclo(3.3.1)nonane; Boc means tert-butoxycarbonyl; (DHQD)₂PHAL means hydroquinidine 1,4-phthalazinediyl diethyl ether; DBU means 1,8-diazabicyclo[5.4.0]undec-7-ene; DIBAL means diisobutylaluminum hydride; DIEA means diisopropylethylamine; DMAP means N,N-dimethylaminopyridine; DMF means N,N-dimethylformamide; dmpe means 1,2-bis(dimethylphosphino)ethane; DMSO means dimethylsulfoxide; dppb means 1,4-bis(diphenylphosphino)-butane; dppe means 1,2-bis(diphenylphosphino)ethane; dppf means 1,1′-bis(diphenylphosphino)ferrocene; dppm means 1,1-bis(diphenylphosphino)methane; EDAC.HCl means 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride; Fmoc means fluorenylmethoxycarbonyl; HATU means O-(7-azabenzotriazol-1-yl)-N,N′N′N′-tetramethyluronium hexafluorophosphate; HMPA means hexamethylphosphoramide; IPA means isopropyl alcohol; MP-BH₃ means macroporous triethylammonium methylpolystyrene cyanoborohydride; TEA means triethylamine; TFA means trifluoroacetic acid; THF means tetrahydrofuran; NCS means N-chlorosuccinimide; NMM means N-methylmorpholine; NMP means N-methylpyrrolidine; PPh₃ means triphenylphosphine.

The following schemes are presented to provide what is believed to be the most useful and readily understood description of procedures and conceptual aspects of this invention. Compounds of this invention may be made by synthetic chemical processes, examples of which are shown herein. It is meant to be understood that the order of the steps in the processes may be varied, that reagents, solvents and reaction conditions may be substituted for those specifically mentioned, and that vulnerable moieties may be protected and deprotected, as necessary.

Schemes

As shown in Scheme 1, compounds of formula (1), wherein R² is as described herein, can be reacted with acids of formula (2); wherein PG is a suitable protecting group and n is 1, 2, or 3, in the presence of a base such as but not limited to diisopropylethylamine, to provide compounds of formula (3). The reaction may involve the use of a carboxyl activating agent such as but not limited to N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride, and a ester activating agent such as but not limited to 1-hydroxybenzotriazole hydrate. The reaction is typically performed at ambient temperature in a solvent such as but not limited to N,N-dimethylformamide, N,N-dimethylacetamide, or mixtures thereof. Compounds of formula (4) can be prepared from compounds of formula (3) after removal of the suitable protecting group using standard reaction conditions known to those skilled in the art and readily available in the literature. Compounds of formula (5), wherein X¹, X², and R¹ are as described herein and X is an appropriate halide, can be reacted with compounds of formula (4) to provide compounds of formula (6) which are representative of compounds of Formula (I). This C—N cross coupling reaction typically employs a base such as but not limited to cesium carbonate, a palladium catalyst such as but not limited to bis(dibenzylideneacetone)palladium(O), and a ligand such as but not limited to (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine). The reaction is typically performed at an elevated temperature in a solvent such as but not limited to dioxane.

tert-Butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate can be reacted with acids of formula (7); wherein n is 1, 2, or 3, in the presence of a base such as but not limited to diisopropylethylamine; to provide compounds of formula (8). The reaction may involve the use of a carboxyl activating agent such as but not limited to N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride, and a ester activating agent such as but not limited to 1-hydroxybenzotriazole hydrate. The reaction is typically performed at ambient temperature in a solvent such as but not limited to N,N-dimethylformamide, N,N-dimethylacetamide, or mixtures thereof. Compounds of formula (9) can be prepared from compounds of formula (8) by reacting the latter with hydrogen in the presence of palladium hydroxide. The reaction is typically performed at ambient temperature in a solvent such as but not limited to tetrahydrofuran. Compounds of formula (5), wherein X¹, X², and R¹ are as described herein and X is an appropriate halide, can be reacted with compounds of formula (9) to provide compounds of formula (10). The C—N cross coupling reaction typically employs a base such as but not limited to cesium carbonate, a palladium catalyst such as but not limited to bis(dibenzylideneacetone)palladium(O), and a ligand such as but not limited to (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine). The reaction is typically performed at an elevated temperature in a solvent such as but not limited to dioxane. Compounds of formula (11) can be prepared by treating compounds of formula (10) with an acid such as but not limited to trifluoroacetic acid in a solvent such as but not limited to dichloromethane. Compounds of formula (13), which are representative of compounds of Formula (I), can be prepared by reacting compounds of formula (11) with compounds of formula (12), wherein R¹⁰ is as described herein, in the presence of a base such as but not limited to diisopropylethylamine. The reaction may involve the use of a carboxyl activating agent such as but not limited to N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride, and a ester activating agent such as but not limited to 1-hydroxybenzotriazole hydrate. The reaction is typically performed at ambient temperature in a solvent such as but not limited to N,N-dimethylformamide, N,N-dimethylacetamide, or mixtures thereof

As shown in Scheme 3, tert-Butyl 4-(4-aminophenyl)piperidine-1-carboxylate can be reacted with acids of formula (7); wherein n is 1, 2, or 3, in the presence of a base such as but not limited to diisopropylethylamine; to provide compounds of formula (14). The reaction may involve the use of a carboxyl activating agent such as but not limited to N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride, and a ester activating agent such as but not limited to 1-hydroxybenzotriazole hydrate. The reaction is typically performed at ambient temperature in a solvent such as but not limited to N,N-dimethylformamide, N,N-dimethylacetamide, or mixtures thereof. Compounds of formula (15) can be prepared from compounds of formula (14) by reacting the latter with hydrogen in the presence of palladium hydroxide. The reaction is typically performed at ambient temperature in a solvent such as but not limited to tetrahydrofuran. Compounds of formula (5), wherein X¹, X², and R¹ are as described herein and X is an appropriate halide, can be reacted with compounds of formula (15) to provide compounds of formula (16). The C—N cross coupling reaction typically employs a base such as but not limited to cesium carbonate, a palladium catalyst such as but not limited to bis(dibenzylideneacetone)palladium(O), and a ligand such as but not limited to (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine). The reaction is typically performed at an elevated temperature in a solvent such as but not limited to dioxane. Compounds of formula (17) can be prepared by treating compounds of formula (16) with an acid such as but not limited to trifluoroacetic acid in a solvent such as but not limited to dichloromethane. Compounds of formula (18), which are representative of compounds of Formula (I), can be prepared by reacting compounds of formula (17) with compounds of formula (12), wherein R¹⁰ is as described herein, in the presence of a base such as but not limited to diisopropylethylamine. The reaction may involve the use of a carboxyl activating agent such as but not limited to N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride, and a ester activating agent such as but not limited to 1-hydroxybenzotriazole hydrate. The reaction is typically performed at ambient temperature in a solvent such as but not limited to N,N-dimethylformamide, N,N-dimethylacetamide, or mixtures thereof. Alternatively, compounds of formula (17) can be reacted with compounds of formula (19), wherein R¹⁰ is as described herein, to provide compounds of formula (20), which are representative of compounds of Formula (I). The reaction is typically performed in the presence of a reducing agent such as but not limited to sodium triacetoxyborohydride and acetic acid in a solvent such as but not limited to methanol and may be performed at an elevated temperature.

EXAMPLES

The following examples are presented to provide what is believed to be the most useful and readily understood description of procedures and conceptual aspects of this invention. Each exemplified compound and intermediate was named using ACD/ChemSketch Version 12.5 (20 Apr. 2011) or (3 Sep. 2012), Advanced Chemistry Development Inc., Toronto, Ontario), or ChemDraw® Ver. 9.0.7 (CambridgeSoft, Cambridge, Mass.).

EXPERIMENTALS Example 1 1-(pyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide Example 1A tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate

1-(Benzyloxycarbonyl)azetidine-3-carboxylic acid (5.10 g, 21.67 mmol), 1-hydroxybenzotriazole hydrate (4.15 g, 27.1 mmol) and tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate (5.28 g, 18.06 mmol) were suspended in dimethylformamide (25 ml) followed by addition of diisopropylethylamine (9.64 ml, 54.2 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (5.19 g, 27.1 mmol). The mixture was stirred at room temperature overnight and the solution was diluted with water. The resulting turbid mixture was extracted with ethyl acetate and then ethyl acetate/tetrahydrofuran. The organics were combined and dried over magnesium sulfate, filtered and concentrated to give a solid which was triturated with ether and filtered to give the title compound.

Example 1B tert-butyl 4-(4-(azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate

tert-Butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate (50 mg, 0.098 mmol) and tetrahydrofuran (5 ml) were added to 20% wet palladium hydroxide on carbon (10 mg, 0.071 mmol) in a 50 ml pressure bottle and the mixture was stirred for 16 hours at 30 psi and room temperature. The mixture was filtered through a nylon membrane and the filtrate was concentrated to give the title compound.

Example 1C tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate

tert-Butyl 4-(4-(azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate (4.97 g, 13.24 mmol), cesium carbonate (10.78 g, 33.1 mmol), 3-bromopyridine (1.307 ml, 13.24 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.764 g, 1.32 mmol) and bis(dibenzylideneacetone)palladium(0) (0.606 g, 0.662 mmol) were suspended in dioxane (50 ml), bubbled with nitrogen for 30 minutes and heated at 100° C. overnight. The mixture was filtered through a celite pad with dichloromethane washes and the filtrate was concentrated. Normal phase chromatography provided the title compound.

Example 1D N-(4-(piperidin-4-yloxy)phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide

tert-Butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate (3.82 g, 8.44 mmol) was dissolved in 60 ml dichloromethane, cooled to 0° C. and treated with trifluoroacetic acid (10 ml). The mixture was allowed to warm to room temperature and was stirred for 2 hours. Removal of the solvent under vacuum provided the title compound.

Example 1E 1-(pyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(4-(piperidin-4-yloxy)phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2-(tetrahydro-2H-pyran-4-yl)acetic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 9.95 (bs, 1H), 7.93 (d, J=4.2 Hz, 1H), 7.88-7.83 (m, 1H), 7.55-7.47 (m, 2H), 7.26-7.08 (m, 1H), 7.01-6.78 (m, 3H), 4.14-4.04 (m, 2H), 4.02-3.62 (m, 6H), 2.37-1.73 (m, 6H), 1.66-1.00 (m, 8H); MS (ESI(+)) m/e 479 (M+H)⁺.

The following Examples were prepared essentially as described in Example 1, substituting the appropriate bromopyridine in Example 1C and the appropriate carboxylic acid in Example 1E. Some products were purified by flash chromatography while others were purified by reverse-phase HPLC. Accordingly, some Examples were isolated as trifluoroacetic acid salts.

TABLE 1 Ex Name ¹H NMR MS 3 N-(4-{[1-(tetrahydro- ¹H NMR (300 MHz, DMSO-d₆) δ ppm 9.96 (s, (ESI(+)) 2H-pyran-4-ylacetyl) 1H), 8.02 (dd, J = 4.3, 1.2 Hz, 1H), 7.55-7.45 m/e 547 piperidin-4-yl]oxy} (m, 3H), 7.15 (d, J = 8.5 Hz, 1H), 6.97-6.90 (m, (M + H)⁺ phenyl)-1-[2- 2H), 4.59-4.47 (m, 1H), 4.28-4.05 (m, 4H), (trifluoromethyl) 3.93-3.53 (m, 6H), 2.27 (d, J = 1.3 Hz, 2H), 2.00- pyridin-3-yl] 1.78 (m, 4H), 1.64-1.38 (m, 5H), 1.39-1.04 (m, 3H) azetidine-3- carboxamide 4 1-(2-methylpyridin- ¹H NMR (300 MHz, DMSO-d₆) δ ppm 9.92 (s, (ESI(+)) 3-yl)-N-(4-{[1- 1H), 7.88 (dd, J = 4.7, 1.4 Hz, 1H), 7.55-7.48 m/e 493 (tetrahydro- (m, 2H), 7.07 (dd, J = 8.0, 4.7 Hz, 1H), 6.97- (M + H)⁺ 2H-pyran-4-ylacetyl) 6.92 (m, 1H), 6.94-6.81 (m, 2H), 4.58-4.47 (m, piperidin-4- 1H), 4.10 (t, J = 7.7 Hz, 2H), 3.98 (t, J = 6.8 Hz, yl]oxy}phenyl) 2H), 3.93-3.50 (m, 6H), 3.29-3.14 (m, 2H), azetidine-3- 2.35 (s, 3H), 2.26 (d, J = 6.9 Hz, 2H), 2.05-1.79 carboxamide (m, 3H), 1.66-1.32 (m, 5H), 1.31-1.06 (m, 2H) 5 1-(4-methylpyridin- ¹H NMR (300 MHz, DMSO-d₆) δ ppm 9.93 (s, (ESI(+)) 3-yl)-N-(4-{[1- 1H), 7.90 (d, J = 4.7 Hz, 1H), 7.76 (s, 1H), 7.55- m/e 493 (tetrahydro- 7.48 (m, 2H), 7.03-6.89 (m, 3H), 4.58-4.47 (m, (M + H)⁺ 2H-pyran-4-ylacetyl) 1H), 4.20-3.95 (m, 4H), 3.95-3.53 (m, 5H), piperidin-4- 3.26-3.15 (m, 4H), 2.26 (d, J = 6.9 Hz, 2H), 2.18 yl]oxy}phenyl) (s, 3H), 2.05-1.78 (m, 3H), 1.66-1.35 (m, 4H), azetidine-3- 1.32-1.08 (m, 2H) carboxamide 6 1-(4-fluoropyridin- ¹H NMR (300 MHz, DMSO-d₆) δ ppm 9.93 (bs, (ESI(+)) 3-yl)-N-(4- 1H), 7.95 (t, J = 11.6 Hz, 2H), 7.55-7.47 (m, m/e 497 {[1-(tetrahydro- 2H), 7.16 (dd, J = 12.7, 5.2 Hz, 1H), 6.97-6.90 (M + H)⁺ 2H-pyran-4-ylacetyl) (m, 2H), 4.59-4.48 (m, 1H), 4.29-4.00 (m, 5H), piperidin-4- 3.93-3.41 (m, 5H), 2.30-2.23 (m, 2H), 1.99-1.78 yl]oxy}phenyl) (m, 4H), 1.66-1.39 (m, 5H), 1.40-1.00 (m, 3H) azetidine-3- carboxamide 7 N-(4-{[1-(tetrahydro- ¹H NMR (300 MHz, DMSO-d₆) δ ppm 9.93 (bs, (ESI(+)) 2H-pyran-4-ylacetyl) 1H), 7.95 (t, J = 11.6 Hz, 2H), 7.55-7.47 (m, m/e 547 piperidin-4- 2H), 7.16 (dd, J = 12.7, 5.2 Hz, 1H), 6.97-6.90 (M + H)⁺ yl]oxy}phenyl)-1-[4- (m, 2H), 4.59-4.48 (m, 1H), 4.29-4.00 (m, 5H), (trifluoromethyl) 3.93-3.41 (m, 5H), 2.30-2.23 (m, 2H), 1.99-1.78 pyridin-3- (m, 4H), 1.66-1.39 (m, 5H), 1.40-1.00 (m, 3H) yl]azetidine-3- carboxamide 31 N-(4-{[1-(2- ¹H NMR (300 MHz, DMSO-d₆) δ ppm 9.94 (s, (ESI(+)) hydroxy-2- 1H), 7.97-7.70 (m, 2H), 7.55-7.47 (m, 2H), m/e 439 methylpropanoyl) 7.18 (dd, J = 8.2, 4.6 Hz, 1H), 7.00-6.78 (m, (M + H)⁺ piperidin- 3H), 5.39 (s, 1H), 4.58-4.41 (m, 1H), 4.09 (t, J = 4-yl]oxy}phenyl)- 7.8 Hz, 2H), 3.95 (t, J = 6.7 Hz, 2H), 3.78-3.47 1-(pyridin-3-yl) (m, 2H), 1.99-1.82 (m, 2H), 1.62-1.34 (m, 2H), azetidine-3- 1.35-1.02 (m, 8H) carboxamide 32 N-[4-({1-[(2S)-2- ¹H NMR (300 MHz, DMSO-d₆) δ ppm 9.94 (s, (ESI(+)) methylbutanoyl] 1H), 7.94 (d, J = 4.7 Hz, 1H), 7.86 (d, J = 2.8 Hz, m/e 437 piperidin-4- 1H), 7.55-7.47 (m, 2H), 7.24-7.04 (m, 1H), (M + H)⁺ yl}oxy)phenyl]- 7.02-6.80 (m, 3H), 4.59-4.48 (m, 1H), 4.09 (t, 1-(pyridin-3-yl) J = 7.8 Hz, 2H), 4.03-3.62 (m, 5H), 3.38 (dd, J = azetidine-3- 13.6, 6.6 Hz, 1H), 2.80-2.64 (m, 1H), 2.01-1.78 carboxamide (m, 2H), 1.64-1.36 (m, 3H), 1.38-1.15 (m, 1H), 1.15-0.86 (m, 4H), 0.81 (t, J = 7.3 Hz, 3H) 33 1-(pyridin-3- ¹H NMR (300 MHz, DMSO-d₆) δ ppm 9.94 (s, (ESI(+)) yl)-N-[4-({1-[(2S)- 1H), 7.98-7.82 (m, 2H), 7.55-7.48 (m, 2H), m/e 451 tetrahydrofuran- 7.20 (dd, J = 8.3, 4.6 Hz, 1H), 7.00-6.80 (m, (M + H)⁺ 2-ylcarbonyl] 3H), 4.67 (t, J = 6.5 Hz, 1H), 4.53 (s, 1H), 4.10 (t, piperidin-4- J = 7.8 Hz, 2H), 3.96 (t, J = 6.6 Hz, 2H), 3.89-3.58 yl}oxy)phenyl] (m, 4H), 3.46-3.08 (m, 4H), 2.12-1.68 (m, 5H), azetidine-3- 1.66-1.38 (m, 2H) carboxamide 34 N-{4-[(1- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) pentanoylpiperidin- (d, J = 5.49 Hz, 1 H) 8.04 (d, J = 2.75 Hz, 1 H) 7.80 m/e 437 4-yl)oxy]phenyl}- (dd, J = 8.85, 5.49 Hz, 1 H) 7.60 (dd, J = 8.39, 2.29 (M + H)⁺ 1-(pyridin-3-yl) Hz, 1 H) 7.51 (d, J = 9.16 Hz. 2 H) 6.96 (d, J = 8.85 azetidine-3- Hz, 2 H) 4.51-4.59 (m, 1 H) 4.25 (t, J = 8.24 Hz, 2 H) carboxamide 4.14 (dd, J = 7.93, 5.80 Hz, 2 H) 3.80-3.90 (m, 1 H) 3.73-3.79 (m, 2 H) 3.31-3.41 (m, 1 H) 3.19-3.27 (m, 1 H) 2.29-2.36 (m, 2 H) 1.83-2.00 (m, 2 H) 1.53-1.62 (m, 1 H) 1.42-1.51 (m, 3 H) 1.24-1.35 (m, 2 H) 0.87 (t, 3 H) 35 N-[4-({1-[(2- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) methylcyclopropyl) (d, J = 5.49 Hz, 1 H) 8.04 (d, J = 2.44 Hz, 1 H) 7.80 m/e 435 carbonyl]piperidin-4- (dd, J = 8.54, 5.49 Hz, 1 H) 7.59 (dd, J = 8.70, 1.98 (M + H)⁺ yl}oxy)phenyl]- Hz, 1 H) 7.52 (d, J = 8.85 Hz, 2 H) 6.97 (d, J = 8.85 1-(pyridin-3-yl) Hz, 2 H) 4.51-4.62 (m, 1 H) 4.25 (t, J = 8.39 Hz, 2 H) azetidine-3- 4.14 (dd, J = 7.93, 5.80 Hz, 2 H) 3.79-4.01 (m, 2 H) carboxamide 3.73-3.78 (m, 1 H) 3.46-3.54 (m, 1 H) 3.16-3.28 (m, 1 H) 1.89 (d, J = 1.53 Hz, 2 H) 1.70- 1.76 (m, 1 H) 1.53 (d, J = 55.85 Hz, 2 H) 1.03- 1.17 (m, 4 H) 0.89-0.97 (m, 1 H) 0.49-0.59 (m, 1 H) 36 N-[4-({1-[(1S,4R)- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) bicyclo[2.2.1] (d, J = 5.19 Hz, 1 H) 8.04 (d, J = 2.75 Hz, 1 H) 7.80 m/e 489 hept-2-ylacetyl] (dd, J = 8.85, 5.49 Hz, 1 H) 7.60 (dd, J = 8.54, 2.14 (M + H)⁺ piperidin-4- Hz, 1 H) 7.47-7.54 (m, 2 H) 6.93-6.99 (m, 2 H) yl}oxy)phenyl]- 4.49-4.58 (m, 1 H) 4.25 (t, J = 8.39 Hz, 2 H) 4.10- 1-(pyridin-3-yl) 4.16 (m, J = 8.09, 5.95 Hz, 2 H) 3.81-3.89 (m, 1 H) azetidine-3- 3.73-3.79 (m, 2 H) 3.18-3.39 (m, 2 H) 2.27-2.36 carboxamide (m, 1 H) 2.11-2.21 (m, 2 H) 1.73-1.99 (m, 4 H) 1.38-1.60 (m, 5 H) 1.34 (d, J = 9.77 Hz, 1 H) 0.97-1.19 (m, 4 H) 37 N-(4-{[1-(4- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) methylpentanoyl) (d, J = 5.19 Hz, 1 H) 8.04 (d, J = 2.75 Hz, 1 H) 7.80 un/e 451 piperidin-4-yl] (dd, J = 8.70, 5.34 Hz, 1 H) 7.59 (dd, J = 8.70, 1.98 (M + H)⁺ oxy}phenyl)- Hz, 1 H) 7.47-7.54 (m, 2 H) 6.93-6.99 (m, 2 H) 1-(pyridin-3-yl) 4.51-4.57 (m, 1 H) 4.25 (t, J = 8.39 Hz, 2 H) 4.10- azetidine-3- 4.16 (m, J = 8.09, 5.95 Hz, 2 H) 3.80-3.87 (m, carboxamide J = 17.70 Hz, 1 H) 3.74-3.79 (m, 2 H) 3.17-3.38 (m, 2 H) 2.27-2.36 (m, J = 8.85, 6.71 Hz, 2 H) 1.83-1.99 (m, J = 22.89 Hz, 2 H) 1.32-1.62 (m, 5 H) 0.87 (d, J = 6.41 Hz, 6 H) 38 N-(4-{[1-(3- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) methylpentanoyl) (d, J = 5.19 Hz, 1 H) 8.05 (d, J = 2.44 Hz, 1 H) 7.80 m/e 451 piperidin-4-yl] (dd, J = 8.85, 5.49 Hz, 1 H) 7.60 (dd, J = 8.54, 2.14 (M + H)⁺ oxy}phenyl)-1- Hz, 1 H) 7.49-7.53 (m, 2 H) 6.93-6.97 (m, 2 H) (pyridin-3-yl) 4.51-4.59 (m, 1 H) 4.25 (t, J = 8.39 Hz, 2 H) 4.14 azetidine-3- (dd, J = 8.09, 5.95 Hz, 2 H) 3.83-3.91 (m, 1 H) carboxamide 3.73-3.79 (m, 2 H) 3.19-3.39 (m, 2 H) 2.27-2.34 (m, 1 H) 2.10-2.18 (m, 1 H) 1.84-1.98 (m, 2 H) 1.73-1.81 (m, 1 H) 1.42-1.59 (m, 2 H) 1.29-1.39 (m, 1 H) 1.11-1.21 (m, 1 H) 0.82-0.89 (m, 6 H) 39 N-(4-{[1-(3- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) ethoxypropanoyl) (d, J = 5.49 Hz, 1 H) 8.05 (d, J = 2.44 Hz, 1 H) 7.80 m/e 453 piperidin-4-yl] (dd, J = 8.54, 5.49 Hz, 1 H) 7.60 (dd, J = 8.85, 1.83 (M + H)⁺ oxy}phenyl)-1- Hz, 1 H) 7.51 (d, J = 9.16 Hz, 2 H) 6.92-6.98 (m, (pyridin-3-yl) 2 H) 4.49-4.59 (m, 1 H) 4.25 (t, J = 8.39 Hz, 2 H) azetidine-3- 4.14 (dd, J = 7.93, 5.80 Hz, 2 H) 3.80-3.89 (m, 1 H) carboxamide 3.74-3.79 (m, 2 H) 3.59 (t, J = 6.56 Hz, 2 H) 3.42 (q, J = 7.02 Hz, 2 H) 3.20-3.38 (m, 2 H) 2.55- 2.63 (m, 2 H) 1.83-1.99 (m, 2 H) 1.41-1.63 (m, 2 H) 1.09 (t, J = 7.02 Hz, 3 H) 40 N-(4-{[1-(2,2- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) dimethylbutanoyl) (d, J = 5.49 Hz, 1 H) 8.05 (d, J = 2.75 Hz, 1 H) 7.81 m/e 451 piperidin-4-yl] (dd, J = 8.54, 5.49 Hz, 1 H) 7.60 (dd, J = 8.85, 1.83 (M + H)⁺ oxy}phenyl)-1- Hz, 1 H) 7.49-7.53 (m, 2 H) 6.96 (d, J = 9.16 Hz, (pyridin-3-yl) 2 H) 4.53-4.59 (m, 1 H) 4.25 (t, J = 8.39 Hz, 2 H) azetidine-3- 4.12-4.18 (m, J = 7.93, 6.10 Hz, 2 H) 3.87-3.93 carboxamide (m, 1 H) 3.75-3.80 (m, 2 H) 3.28-3.38 (m, 2 H) 1.89-1.97 (m, 2 H) 1.60 (q, J = 7.53 Hz, 2 H) 1.46- 1.54 (m, 2 H) 1.16 (s, 6 H) 0.80 (t, J = 7.48 Hz, 3 H) 41 N-(4-{[1-(3,3- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) dimethylbutanoyl) (d, J = 5.49 Hz, 1 H) 8.05 (d, J = 2.44 Hz, 1 H) 7.80 m/e 451 piperidin-4-yl] (dd, J = 8.54, 5.49 Hz, 1 H) 7.60 (dd, J = 8.70, 1.98 (M + H)⁺ oxy}phenyl)-1- Hz, 1 H) 7.49-7.52 (m, 2 H) 6.92-6.99 (m, 2 H) (pyridin-3-yl) 4.47-4.58 (m, 1 H) 4.22-4.29 (m, 2 H) 4.14 (dd, azetidine-3- J = 8.09, 5.95 Hz, 2 H) 3.85-3.92 (m, 1 H) 3.74- carboxamide 3.80 (m, 2 H) 3.34-3.43 (m, 1 H) 3.20-3.27 (m, 1 H) 2.26 (s, 2 H) 1.82-2.01 (m, 2 H) 1.38-1.60 (m, 2 H) 0.99 (s, 9 H) 42 N-(4-{[1-(2,2- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) dimethylpropanoyl) (d, J = 5.49 Hz, 1 H) 8.04 (d, J = 2.44 Hz, 1 H) 7.80 m/e 437 piperidin-4-yl]oxy} (dd, J = 8.54, 5.49 Hz, 1 H) 7.59-7.61 (m, 1 H) (M + H)⁺ phenyl)-1- 7.49-7.54 (m, 2 H) 6.93-6.98 (m, 2 H) 4.51-4.61 (pyridin-3-yl) (m, 1 H) 4.25 (t, J = 8.39 Hz, 2 H) 4.14 (dd, azetidine-3- J = 8.09, 5.95 Hz, 2 H) 3.85-3.92 (m, 2 H) 3.73- carboxamide 3.79 (m, 1 H) 3.29-3.38 (m, 2 H) 1.89-1.99 (m, 2 H) 1.45-1.56 (m, 2 H) 1.20 (s, 9 H) 43 N-{4-[(1- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) butanoylpiperidin- (d, J = 5.49 Hz, 1 H) 8.05 (d, J = 2.44 Hz, 1 H) 7.80 m/e 423 4-yl)oxy]phenyl}- (dd, J = 8.54, 5.49 Hz, 1 H) 7.60 (dd, J = 8.85, 1.83 (M + H)⁺ 1-(pyridin-3-yl) Hz, 1 H) 7.49-7.53 (m, 2 H) 6.93-6.98 (m, 2 H) azetidine- 4.49-4.60 (m, 1 H) 4.25 (t, J = 8.39 Hz, 2 H) 4.14 3-carboxamide (dd, J = 7.93, 6.10 Hz, 2 H) 3.82-3.90 (m, 1 H) 3.73-3.79 (m, 2 H) 3.20-3.37 (m, 2H) 2.31 (t, J = 7.17 Hz, 2 H) 1.82-1.98 (m, 2 H) 1.41-1.63 (m, 4 H) 0.89 (t, J = 7.32 Hz, 3 H) 44 N-(4-{[1- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) (ethoxyacetyl) (d, J = 5.49 Hz, 1 H) 8.05 (d, J = 2.44 Hz, 1 H) 7.80 m/e 439 piperidin-4- (dd, J = 8.54, 5.49 Hz, 1 H) 7.60 (dd, J = 8.54, 1.83 (M + H)⁺ yl]oxy}phenyl)- Hz, 1 H) 7.51 (d, J = 9.16 Hz, 2 H) 6.96 (d, J = 9.16 1-(pyridin-3- yl) Hz, 2 H) 4.50-4.59 (m, 1 H) 4.25 (t, J = 8.39 Hz, 2 azetidine-3- H) 4.10-4.16 (m, 4 H) 3.80-3.87 (m, 1 H) 3.73-3.78 carboxamide (m, 2 H) 3.47 (q, J = 7.02 Hz, 2 H) 3.20-3.35 (m, 2 H) 1.86-1.98 (m, J = 21.67 Hz, 2 H) 1.45- 1.64 (m, 2 H) 1.13 (t, J = 7.02 Hz, 3 H) 45 N-(4-{[1-(3- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) methylbutanoyl) (d, J = 5.49 Hz, 1 H) 8.05 (d, J = 2.44 Hz, 1 H) 7.80 m/e 437 piperidin-4-yl] (dd, J = 8.85, 5.49 Hz, 1 H) 7.60 (dd, J = 8.70, 1.98 (M + H)⁺ oxy}phenyl)-1- Hz, 1 H) 7.47-7.55 (m, 2 H) 6.93-6.98 (m, 2 H) (pyridin-3- yl) 4.51-4.57 (m, 1 H) 4.25 (t, J = 8.39 Hz, 2 H) 4.14 azetidine-3- (dd, J = 7.93, 6.10 Hz, 2 H) 3.83-3.90 (m, 1 H) carboxamide 3.74-3.79 (m, 2 H) 3.19-3.37 (m, 2 H) 2.19-2.24 (m, 2 H) 1.82-2.03 (m, 3 H) 1.41-1.60 (m, 2 H) 0.90 (d, J = 6.71 Hz, 6 H) 46 N-(4-{[1-(2- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) methylpropanoyl) (d, J = 5.49 Hz, 1 H) 8.05 (d, J = 2.44 Hz, 1 H) 7.80 m/e 423 piperidin-4-yl] (dd, J = 8.54, 5.49 Hz, 1 H) 7.60 (dd, J = 8.70, 1.98 (M + H)⁺ oxy}phenyl)-1- Hz, 1 H) 7.49-7.54 (m, 2 H) 6.93-6.99 (m, 2 H) (pyridin-3-yl) 4.52-4.60 (m, 1 H) 4.25 (t, J = 8.24 Hz, 2 H) 4.14 azetidine-3- (dd, J = 7.93, 6.10 Hz, 2 H) 3.84 (s, 1 H) 3.75-3.79 carboxamide (m, 2 H) 3.18-3.42 (m, 2 H) 2.86-2.93 (m, 1 H) 1.84-1.99 (m, 2 H) 1.42-1.63 (m, 2 H) 1.00 (d, J = 6.71 Hz, 6 H) 47 N-(4-{[1-(N- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) acetyl-L-leucyl) (d, J = 5.49 Hz, 1 H) 8.05 (d, J = 2.75 Hz, 1 H) 7.81 m/e 508 piperidin-4- (dd, J = 8.54, 5.49 Hz, 1 H) 7.60 (dd, J = 8.85, 1.83 (M + H)⁺ yl]oxy}phenyl)- Hz, 1 H) 7.52 (d, J = 8.85 Hz, 2 H) 6.95-6.99 (m, 1-(pyridin-3-yl) 2 H) 4.77 (dd, J = 9.00, 3.81 Hz, 1 H) 4.53-4.62 azetidine-3- (m, 1 H) 4.25 (t, J = 8.39 Hz, 2 H) 4.12-4.17 (m, 2 carboxamide H) 3.92 (d, J = 13.12 Hz, 1 H) 3.74-3.79 (m, 2 H) 3.31-3.47 (m, 2 H) 3.14-3.21 (m, 1 H) 1.92-2.01 (m, 1 H) 1.85 (s, 3 H) 1.28-1.63 (m, 5 H) 0.85-0.91 (m, 6 H) 48 N-[4-({1-[(2- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) methoxyethoxy) (d, J = 5.19 Hz, 1 H) 8.05 (d, J = 2.44 Hz, 1 H) 7.80 m/e 469 acetyl]piperidin-4- (dd, J = 8.85, 5.49 Hz, 1 H) 7.60 (dd, J = 8.54, 2.14 (M + H)⁺ yl}oxy)phenyl]- Hz, 1 H) 7.51 (d, J = 9.16 Hz, 2 H) 6.93-6.99 (m, 1-(pyridin-3-yl) J = 9.61, 9.61 Hz, 2 H) 4.51-4.59 (m, 1 H) 4.25 (t, azetidine-3- J = 8.39 Hz, 2 H) 4.09-4.18 (m, 4 H) 3.80-3.86 carboxamide (m, 1 H) 3.74-3.77 (m, 1 H) 3.54-3.57 (m, 2 H) 3.47 (dd, J = 5.65, 3.51 Hz, 2 H) 3.20-3.33 (m, 6 H) 1.87-1.96 (m, 2 H) 1.45-1.66 (m, 2 H) 49 N-(4-{[1- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) (cyclohexylcarbonyl) (d, J = 5.49 Hz, 1 H) 8.05 (d, J = 2.75 Hz, 1 H) 7.80 m/e 463 piperidin-4-yl]oxy} (dd, J = 8.54, 5.49 Hz, 1 H) 7.60 (dd, J = 8.70, 1.98 (M + H)⁺ phenyl)-1-(pyridin- Hz, 1 H) 7.51 (d, J = 8.85 Hz, 2 H) 6.94-6.97 (m, 3-yl)azetidine-3- 2 H) 4.49-4.58 (m, 1 H) 4.25 (t, J = 8.24 Hz, 2 H) carboxamide 4.14 (dd, J = 8.09, 5.95 Hz, 2 H) 3.84 (dd, 1 H) 3.73-3.78 (m, 2 H) 3.33-3.40 (m, J = 9.77 Hz, 1 H) 3.17-3.27 (m, 1 H) 2.58-2.63 (m, 1 H) 1.82- 1.99 (m, 2 H) 1.09-1.73 (m, 12 H) 50 N-(4-{[1- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) (cyclohexylacetyl) (d, J = 5.49 Hz, 1 H) 8.05 (d, J = 2.44 Hz, 1 H) 7.81 m/e 477 piperidin-4-yl]oxy} (dd, J = 8.85, 5.49 Hz, 1 H) 7.60 (dd, J = 8.85, 1.83 (M + H)⁺ phenyl)-1- Hz, 1 H) 7.48-7.53 (m, 2 H) 6.91-7.00 (m, 2 H) (pyridin-3-yl) 4.51-4.57 (m, 1 H) 4.25 (t, J = 8.24 Hz, 2 H) 4.14 azetidine-3- (dd, J = 7.93, 6.10 Hz, 2 H) 3.84 (d, J = 4.27 Hz, 1 carboxamide H) 3.74-3.79 (m, 2 H) 3.31-3.38 (m, 1 H) 3.16- 3.27 (m, 1 H) 2.18-2.23 (m, J = 6.56, 2.90 Hz, 2 H) 1.83-1.97 (m, 2 H) 1.41-1.71 (m, 8 H) 1.06- 1.27 (m, 3 H) 0.88-0.98 (m, 2 H) 51 1-(pyridin-3- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) yl)-N-(4-{[1-(4,4,4- (d, J = 5.49 Hz, 1 H) 8.05 (d, J = 2.44 Hz, 1 H) 7.80 m/e 477 trifluorobutanoyl) (dd, J = 8.85, 5.49 Hz, 1 H) 7.59 (dd, J = 8.70, 1.98 (M + H)⁺ piperidin-4-yl]oxy} Hz, 1 H) 7.49-7.54 (m, 2 H) 6.93-6.99 (m, 2 H) phenyl)azetidine-3- 4.52-4.60 (m, 1 H) 4.25 (t, J = 8.39 Hz, 2 H) 4.14 carboxamide (dd, J = 8.09, 5.95 Hz, 2 H) 3.81-3.89 (m, 1 H) 3.74-3.78 (m, 2 H) 3.25-3.39 (m, 2 H) 2.61- 2.68 (m, 2 H) 2.43-2.51 (m, 2 H) 1.84-2.00 (m, 2 H) 1.44-1.65 (m, 2 H) 52 N-(4-{[1- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) (cyclopentylcarbonyl) (d, J = 5.49 Hz, 1 H) 8.05 (d, J= 2.75 Hz, 1 H) 7.80 m/e 449 piperidin-4-yl]oxy} (dd, J = 8.54, 5.49 Hz, 1 H) 7.60 (dd, J = 8.70, 1.98 (M + H)⁺ phenyl)-1-(pyridin-3- Hz, 1 H) 7.51 (d, J = 8.85 Hz , 2 H) 6.96 (d, J = 8.85 yl)azetidine-3- Hz, 2 H) 4.51-4.59 (m, 1 H) 4.25 (t, J = 8.39 Hz, 2 carboxamide H) 4.09-4.18 (m, 2 H) 3.81-3.90 (m, 1 H) 3.75- 3.79 (m, 2 H) 3.33-3.42 (m, 1 H) 3.20-3.29 (m, 1 H) 2.96-3.02 (m, 1 H) 1.46-1.98 (m, 12 H) 53 N-[4-({1-[(1- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) methylcyclohexyl) (d, J = 5.19 Hz, 1 H) 8.04 (d, J = 2.44 Ha, 1 H) 7.79 m/e 477 carbonyl] (dd, J = 8.54, 5.49 Hz, 1 H) 7.59 (dd, J = 8.70, 1.98 (M + H)⁺ piperidin-4- Hz, 1 H) 7.49-7.53 (m, 2 H) 6.96 (d, J = 8.85 Hz, yl}oxy)phenyl]- 2 H) 4.50-4.59 (m, 1 H) 4.25 (t, J = 8.39 Hz, 2 H) 1-(pyridin-3-yl) 4.14 (dd, J = 7.93, 6.10 Hz, 2 H) 3.90 (dd, J = 9.00, azetidine-3- 5.95 Hz, 2 H) 3.74-3.78 (m, 1 H) 3.27-3.36 (m, carboxamide 2 H) 1.85-1.99 (m, 4 H) 1.24-1.55 (m, 10 H) 1.18 (s, 3 H) 54 N-(4-{[1- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) (furan-3-ylcarbonyl) (d, J = 5.49 Hz, 1 H) 8.04 (d, J = 2.44 Ha, 1 H) 8.02 m/e 447 piperidin-4-yl] (s, 1 H) 7.80 (dd, J = 8.85, 5.49 Hz, 1 H) 7.71- (M + H)⁺ oxy}phenyl)-1- 7.73 (m, 1 H) 7.59 (dd, J = 8.70, 2.29 Hz, 1 H) 7.52 (pyridin-3-yl) (d, J = 8.85 Hz, 2 H) 6.97 (d, J= 8.85 Hz, 2 H) 6.67 azetidine-3- (s, 1 H) 4.56-4.62 (m, 1 H) 4.25 (t, J = 8.24 Hz, 2 carboxamide H) 4.14 (dd, J = 7.93, 6.10 Hz, 2 H) 3.82-3.92 (m, 2 H) 3.73-3.77 (m, 1 H) 3.39-3.49 (m, 2 H) 1.91-2.00 (m, 2 H) 1.55-1.65 (m, 2 H) 55 1-(pyridin-3- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.09 (ESI(+)) yl)-N-(4-{[1-(3,3,3- (d, J = 4.58 Hz, 1 H) 8.02 (s, 1 H) 7.73 (dd, J = 8.54, m/e 463 trifluoropropanoyl) 5.49 Hz, 1 H) 7.48-7.54 (m, J = 9.16 Hz, 3 H) (M + H)⁺ piperidin-4-yl]oxy} 6.96 (d, J = 8.85 Hz, 2 H) 4.57 (s, 1 H) 4.23 (t, phenyl)azetidine-3- J = 8.24 Hz, 2 H) 4.09-4.14 (m, 2 H) 3.80-3.87 carboxamide (m, 1 H) 3.72-3.78 (m, 2 H) 3.59-3.63 (m, 2 H) 3.26-3.39 (m, 2 H) 1.93 (s, 2 H) 1.51 (s, 2 H) 56 N-{4-[(1- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) acetylpiperidin-4- (d, J = 5.19 Hz, 1 H) 8.05 (d, J = 2.75 Hz, 1 H) 7.81 m/e 395 yl)oxy]phenyl}-1- (dd, J = 8.85, 5.49 Hz, 1 H) 7.60 (dd, J = 8.70, 1.98 (M + H)⁺ (pyridin-3-yl) Hz, 1 H) 7.49-7.53 (m, 2 H) 6.92-6.98 (m, 2 H) azetidine-3- 4.50-4.58 (m, 1 H) 4.25 (t, J = 8.39 Hz, 2 H) 4.14 carboxamide (dd, J = 7.93, 6.10 Hz, 2 H) 3.79-3.85 (m, 1 H) 3.75-3.79 (m, 2 H) 3.19-3.40 (m, 2 H) 2.02 (s, 3 H) 1.83-1.99 (m, 2 H) 1.41-1.68 (m, 2 H) 57 N-(4-{[1- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) (methoxyacetyl) (d, J = 5.49 Hz, 1 H) 8.05 (d, J = 2.44 Hz, 1 H) 7.80 m/e 425 piperidin-4-yl] (dd, J = 8.54, 5.49 Hz, 1 H) 7.60 (dd, J = 8.54, 2.44 (M + H)⁺ oxy}phenyl)-1- Hz, 1 H) 7.51 (d, J = 9.16 Hz, 2 H) 6.96 (d, J = 9.16 (pyridin-3-yl) Hz, 2 H) 4.51-4.59 (m, 1 H) 4.25 (t, J = 8.39 Hz, 2 azetidine-3- H) 4.14 (dd, J = 8.09, 5.95 Hz, 2 H) 4.10 (d, J = 3.05 carboxamide Hz, 2 H) 3.80-3.86 (m, 1 H) 3.74-3.77 (m, 1 H) 3.57-3.64 (m, 1 H) 3.18-3.34 (m, 5 H) 1.85-1.99 (m, 2 H) 1.44-1.64 (m, 2 H) 58 1-(pyridin-3- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.11 (ESI(+)) yl)-N-(4-{[1- (d, J = 5.49 Hz, 1 H) 8.05 (d, J = 2.75 Hz, 1 H) 7.76- m/e 463 (thiophen-3- 7.78 (m, 1 H) 7.59-7.61 (m, 2 H) 7.52 (d, (M + H)⁺ ylcarbonyl) J = 8.85 Hz, 2 H) 7.44 (d, J = 4.88 Hz, 1 H) 7.22 (d, piperidin-4- J = 5.19 Hz, 1 H) 6.97 (d, J = 9.16 Hz, 2H) 4.56- yl]oxy}phenyl) 4.62 (m, 1 H) 4.25 (t, J = 8.39 Hz, 2 H) 4.12-4.16 azetidine-3- (m, 2 H) 3.87-3.96 (m, 1 H) 3.72-3.79 (m, 2 H) carboxamide 3.33-3.46 (m, 2 H) 1.90-2.01 (m, J = 1.83 Hz, 2 H) 1.54-1.70 (m, 2 H) 59 N-[4-({1-[(3- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) methylthiophen-2- (d, J = 5.49 Hz, 1 H) 8.04 (d, J = 2.75 Hz, 1 H) 7.80 m/e 477 yl)carbonyl] (dd, J = 8.54, 5.49 Hz, 1 H) 7.48-7.62 (m, 4 H) (M + H)⁺ piperidin-4- 6.93-6.99 (m, 3 H) 4.54-4.66 (m, 1 H) 4.25 (t, yl}oxy)phenyl]- J = 8.39 Hz, 2 H) 4.14 (dd, J = 7.93, 6.10 Hz, 2 H) 1-(pyridin-3-yl) 3.72-3.85 (m, 3 H) 3.34-3.45 (m, 2 H) 2.20 (s, 3 azetidine-3- H) 1.91-2.00 (m, J = 9.77 Hz, 2 H) 1.53-1.64 (m, carboxamide 2 H) 60 N-(4-{[1- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.13 (ESI(+)) (morpholin-4- (d, J = 5.49 Hz, 1 H) 8.05 (d, J = 2.44 Hz, 1 H) 7.80 m/e 480 ylacetyl)piperidin-4- (dd, J = 8.85, 5.49 Hz, 1 H) 7.60 (dd, J = 8.54, 2.14 (M + H)⁺ yl]oxy}phenyl)-1- Hz, 1 H) 7.53 (d, J = 8.85 Hz, 2 H) 6.97 (d, J = 9.16 (pyridin-3-yl) Hz, 2 H) 4.54-4.64 (m, 1 H) 4.35 (s, 2 H) 4.25 (t, azetidine-3- J = 8.39 Hz, 2 H) 4.14 (dd, J = 8.09, 5.95 Hz, 2 H) carboxamide 3.76-4.04 (m, 6 H) 3.52-3.60 (m, 1 H) 3.25- 3.49 (m, 4 H) 3.08-3.22 (m, 2 H) 1.89-2.08 (m, 2 H) 1.50-1.77 (m, 2 H) 61 1-(pyridin-3- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) y1)-N-(4-{[1- (d, J = 5.49 Hz, 1 H) 8.04 (d, J = 1.83 Hz, 1 H) 7.79 m/e 463 (thiophen-2- (dd, J = 8.85, 5.49 Hz, 1 H) 7.58 (dd, J = 8.54, 2.14 (M + H)⁺ ylcarbonyl) Hz, 1 H) 7.52 (d, J = 9.16 Hz, 2 H) 7.42 (d, J = 3.66 piperidin-4-yl] Hz, 1 H) 7.18-7.22 (m, 1 H) 7.14 (dd, J = 4.88, oxy}phenyl) 3.66 Hz, 1 H) 6.99 (d, 2 H) 4.58-4.66 (m, 1 H) azetidine-3- 4.25 (t, J = 8.24 Hz, 2 H) 4.14 (dd, J = 7.93, 6.10 Hz, carboxamide 2 H) 3.89-3.96 (m, 2 H) 3.74-3.80 (m, 1 H) 3.52 (m, 2 H) 1.95-2.04 (m, 2 H) 1.59-1.70 (m, 2 H) 62 N-[4-({1-[(5- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) methylthiophen-2- (d, J = 5.49 Hz, 1 H) 8.04 (d, J = 2.75 Hz, 1 H) 7.80 m/e 477 yl)carbonyl] (dd, J = 8.54, 5.49 Hz, 1 H) 7.59 (dd, J = 8.24, 2.14 (M + H)⁺ piperidin-4- Hz, 1 H) 7.52 (d, J = 9.16 Hz, 2 H) 7.23 (d, J = 3.36 yl}oxy)phenyl]- Hz, 1 H) 6.98 (d, J = 9.16 Hz, 2 H) 6.80-6.86 (m, 1-(pyridin-3-yl) 1 H) 4.56-4.65 (m, 1 H) 4.25 (t, J = 8.39 Hz, 2 H) azetidine-3- 4.12-4.17 (m, 2 H) 3.90-3.95 (m, 2 H) 3.74- carboxamide 3.79 (m, 1 H) 3.45-3.55 (m, 2 H) 2.47 (s, 3 H) 1.94-2.05 (m, 2 H) 1.58-1.67 (m, 2 H) 63 N-(4-{[1- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) (furan-2- (d, J = 5.49 Hz, 1 H) 8.05 (d, J = 2.44 Hz, 1 H) 7.78- m/e 447 ylcarbonyl) 7.83 (m, 2 H) 7.60 (dd, J = 8.39, 2.29 Hz, 1 H) (M + H)⁺ piperidin-4-yl] 7.52 (d, J = 9.16 Hz, 2 H) 6.96-7.02 (m, 3 H) 6.63 oxy}phenyl)- (dd, J = 3.36, 1.83 Hz, 1 H) 4.58-4.67 (m, 1 H) 1-(pyridin-3- 4.25 (t, J = 8.39 Hz, 2 H) 4.14 (dd, J = 7.93, 5.80 Hz, yl)azetidine-3- 2 H) 3.92-3.99 (m, 2 H) 3.75-3.80 (m, 1 H) carboxamide 3.41-3.59 (m, 2 H) 1.95-2.04 (m, 2 H) 1.58-1.67 (m, 2 H) 64 N-[4-({1-[(1- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.11 (ESI(+)) methyl-1H- (s, 1 H) 8.04 (d, J = 2.44 Hz, 1 H) 7.80 (dd, J = 8.70 m/e 460 pyrrol-2-yl) 5.34 Hz, 1 H) 7.59 (dd, J = 8.85, 1.83 Hz, 1 H) 7.52 (M + H)⁺ carbonyl] (d, J = 9.16 Hz, 2 H) 6.97 (d, J = 9.16 Hz, 2 H) 6.88 piperidin-4- (s, 1 H) 6.33 (dd, J = 3.81, 1.68 Hz, 1 H) 6.01- yl}oxy)phenyl]- 6.05 (m, 1 H) 4.52-4.63 (m, 1 H) 4.25 (t, J = 8.39 1-(pyridin-3-yl) Hz, 2 H) 4.11-4.17 (m, 2 H) 3.90-3.96 (m, 2 H) azetidine-3- 3.74-3.79 (m, 1 H) 3.66 (s, 3 H) 3.41-3.50 (m, 2 carboxamide H) 1.91-2.04 (m, 2 H) 1.52-1.67 (m, 2 H) 65 N-{4-[(1- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) propanoylpiperidin- (d, J = 5.49 Hz, 1 H) 8.05 (d, J = 2.75 Hz, 1 H) 7.80 m/e 409 4-yl)oxy]phenyl}- (dd, J = 8.85, 5.49 Hz, 1 H) 7.60 (dd, J = 8.39, 2.29 (M + H)⁺ 1-(pyridin-3-yl) Hz, 1 H) 7.51 (d, J = 8.85 Hz, 2 H) 6.96 (d, 2 H) azetidine-3- 4.48-4.60 (m, 1 H) 4.25 (t, J = 8.39 Jz, 2 H) 4.14 carboxamide (dd, J = 7.93, 6.10 Hz, 2 H) 3.81-3.90 (m, 1 H) 3.72-3.80 (m, 2 H) 3.17-3.41 (m, 2 H) 2.34 (q, J = 7.53 Hz, 2 H) 1.82-2.01 (m, 2 H) 1.35-1.63 (m, 2 H) 1.00 (t, J = 7.48 Hz, 3 H) 66 N-[4-({1-[(1- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) methylcyclopropyl) (d, J = 5.49 Hz, 1 H) 8.05 (d, J = 2.75 Hz, 1 H) 7.80 m/e 435 carbonyl] (dd, J = 8.85, 5.49 Hz, 1 H) 7.60 (dd, J = 8.55, 1.83 (M + H)⁺ piperidin-4- Hz, 1 H) 7.52 (d, J = 8.85 Hz, 2 H) 6.96 (d, J = 8.85 yl}oxy)phenyl]- Hz, 2 H) 4.51-4.60 (m, 1 H) 4.25 (t, J = 8.39 Hz, 2 1-(pyridin-3-yl) H) 4.14 (dd, J = 7.93, 5.80 Hz, 2 H) 3.82-3.92 (m, azetidine-3- 2 H) 3.74-3.78 (m, 1 H) 3.31-3.46 (m, 2 H) carboxamide 1.85-1.96 (m, 2 H) 1.47-1.58 (m, J = 7.32 Hz, 2 H) 1.23 (s, 3 H) 0.76-0.81 (m, 2 H) 0.52-0.56 (m, 2 H) 67 N-(4-{[1- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 N/A (N,N-dimethyl-beta- (d, J = 5.19 Hz, 1 H) 8.05 (d, J = 2.75 Hz, 1 H) 7.80 alanyl)piperidin-4- (dd, J = 8.85, 5.49 Hz, 1 H) 7.60 (dd, J = 8.39, 2.29 yl]oxy}phenyl)-1- Hz, 1 H) 7.53 (d, J = 9.16 Hz, 2 H) 6.99 (d, J = 8.85 (pyridin-3-yl) Hz, 2 H) 4.56-4.64 (m, 1 H) 4.25 (t, J = 8.39 Hz, 2 azetidine-3- H) 4.14 (dd, J = 7.93, 5.80 Hz, 2 H) 3.72-3.82 (m, carboxamide 3 H) 3.67-3.70 (m, 2 H) 3.19-3.54 (m, J = 87.28 Hz, 4 H) 2.92 (d, J = 10.68 Hz, 6 H) 1.97-2.16 (m, 2 H) 1.66-1.85 (m, 2 H) 68 1-(pyridin-3- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) yl)-N-(4-{[1- (d, J = 5.49 Hz, 1 H) 8.05 (d, J = 2.44 Hz, 1 H) 7.98- m/e 464 (1,3-thiazol-2- 8.02 (m, 2 H) 7.81 (dd, J = 8.85, 5.49 Hz, 1 H) (M + H)⁺ ylcarbonyl) 7.60 (dd, J = 8.39, 2.29 Hz, 1 H) 7.53 (d, 2 H) 6.99 piperidin-4- (d, 2 H) 4.55-4.69 (m, 2 H) 4.25 (t, J = 8.39 Hz, 2 yl]oxy}phenyl) H) 4.15 (dd, J = 7.93, 5.80 Hz, 2 H) 3.94-4.08 (m, azetidine-3- J = 41.20, 9.46 Hz, 2 H) 3.74-3.79 (m, 1 H) 3.49- carboxamide 3.58 (m, 1 H) 1.98-2.08 (m, 2 H) 1.67 (s, 2 H) 69 N-(4-1{[1- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) (cyclopentylacetyl) (d, J = 5.49 Hz, 1 H) 8.05 (d, J = 2.44 Hz, 1 H) 7.77- m/e 463 piperidin-4- 7.82 (m, 1 H) 7.60 (dd, J = 8.70, 1.98 Hz, 1 H) (M + H)⁺ yl]oxy}phenyl)- 7.51 (d, J = 8.85 Hz, 2 H) 6.96 (d, J = 8.85 Hz, 2 H) 1-(pyridin-3-yl) 4.50-4.58 (m, 1 H) 4.25 (t, J = 8.39 Hz, 2 H) 4.11- azetidine-3- 4.15 (m, 2 H) 3.81-3.90 (m, 1 H) 3.73-3.79 carboxamide (m, 2 H) 3.18-3.40 (m, 2 H) 2.35 (dd, J = 7.17, 2.59 Hz, 2 H) 2.05-2.16 (m, 1 H) 1.83-1.98 (m, 2 H) 1.68-1.77 (m, 2 H) 1.42-1.63 (m, 6 H) 1.05-1.19 (m, 2 H) 70 N-(4-{[1-(2,3- ¹H NMR (500 MHz, DMSO-d₆/D₂O) δ ppm 8.12 (ESI(+)) dimethylbutanoyl) (d, J = 5.49 Hz, 1 H) 8.05 (d, J = 2.44 Hz, 1 H) 7.80 m/e 451 piperidin-4- (dd, J = 8.85, 5.49 Hz, 1 H) 7.60 (dd, J = 8.70, 2.29 (M + H)⁺ yl]oxy}phenyl)- Hz, 1 H) 7.50-7.53 (m, 2 H) 6.96 (d, J = 9.16 Hz, 1-(pyridin-3- 2 H) 4.50-4.61 (m, 1 H) 4.25 (t, J = 8.39 Hz, 2 H) yl)azetidine-3- 4.14 (dd, J = 8.09, 5.95 Hz, 2 H) 3.92-3.97 (m, 1 carboxamide H) 3.74-3.87 (m, 3 H) 3.20-3.43 (m, 2 H) 2.55- 2.61 (m, 1 H) 1.38-2.03 (m, 5 H) 0.95 (d, J = 6.71 Hz, 2 H) 0.81-0.88 (m, 6 H)

Example 8 tert-butyl 4-[4-({[(3S)-1-(pyridin-3-yl)pyrrolidin-3-yl]carbonyl}amino)phenoxy]piperidine-1-carboxylate

The title compound was prepared as described in Example 1A-C, substituting (S)-1-(benzyloxycarbonyl)pyrrolidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid in Example 1A. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 9.96 (s, 1H), 7.95 (d, J=2.9 Hz, 1H), 7.85 (dd, J=4.6, 1.3 Hz, 1H), 7.54-7.48 (m, 2H), 7.15 (dd, J=8.4, 4.6 Hz, 1H), 6.98-6.86 (m, 3H), 4.53-4.41 (m, 1H), 3.73-3.46 (m, 3H), 3.45-3.30 (m, 2H), 3.24 (dd, J=17.5, 10.0 Hz, 2H), 3.12 (dd, J=24.9, 15.2 Hz, 2H), 2.35-2.10 (m, 2H), 2.01-1.78 (m, 2H), 1.68-1.42 (m, 2H), 1.40 (s, 9H); MS (ESI(+)) m/e 467 (M+H)⁺.

Example 9 tert-butyl 4-[4-({[(3R)-1-(pyridin-3-yl)pyrrolidin-3-yl]carbonyl}amino)phenoxy]piperidine-1-carboxylate

The title compound was prepared as described in Example 1A-C, substituting (R)-1-(benzyloxycarbonyl)pyrrolidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid in Example 1A. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 9.97 (s, 1H), 7.95 (d, J=2.9 Hz, 1H), 7.85 (dd, J=4.6, 1.3 Hz, 1H), 7.54-7.48 (m, 2H), 7.16 (dd, J=8.4, 4.6 Hz, 1H), 6.98-6.86 (m, 3H), 4.53-4.41 (m, 1H), 3.75-3.45 (m, 3H), 3.45-3.34 (m, 3H), 3.25 (dd, J=8.8, 6.2 Hz, 1H), 3.23-3.09 (m, 2H), 2.34-2.07 (m, 2H), 1.95-1.75 (m, 2H), 1.59-1.41 (m, 2H), 1.40 (s, 9H); MS (ESI(+)) m/e 467 (M+H)⁺.

Example 10 1-(pyridin-3-yl)-N-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl} phenyl)azetidine-3-carboxamide Example 10A tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting tert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate.

Example 10B tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1B, substituting tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 10C tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1C, substituting tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 10D N-(4-(piperidin-4-yl)phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 10E 1-(pyridin-3-yl)-N-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(4-(piperidin-4-yl)phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and (S)-tetrahydrofuran-2-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.01 (s, 1H), 7.93 (dd, J=4.6, 1.3 Hz, 1H), 7.85 (d, J=2.8 Hz, 1H), 7.57-7.49 (m, 2H), 7.22-7.14 (m, 3H), 6.86 (ddd, J=8.2, 2.9, 1.4 Hz, 1H), 4.68 (dd, J=7.5, 5.7 Hz, 1H), 4.53-4.43 (m, 1H), 4.10 (d, J=8.0 Hz, 2H), 3.95 (d, J=13.3 Hz, 2H), 3.89-3.64 (m, 3H), 3.15-3.00 (m, 1H), 2.82-2.59 (m, 2H), 2.19-1.68 (m, 6H), 1.61-1.29 (m, 3H); MS (ESI(+)) m/e 435 (M+H)⁺.

The following Examples were prepared essentially as described in Example 10, substituting the appropriate bromopyridine in Example 10C and the appropriate carboxylic acid in Example 10E. Some products were purified by flash chromatography while others were purified by reverse-phase HPLC. Accordingly, some Examples were isolated as trifluoroacetic acid salts.

TABLE 2 Ex Name ¹H NMR MS 2 1-(2-cyanopyridin-3- ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.04 (s, (ESI(+)) yl)-N-{4-[1-(2- 1H), 8.12-7.94 (m, 1H), 7.54 (d, J = 8.5 Hz, m/e 448 hydroxy-2- 2H), 7.48-7.37 (m, 1H), 7.21-7.16 (m, 2H), (M + H)⁺ methylpropanoyl) 7.14 (dt, J = 7.7, 1.9 Hz, 1H), 5.36 (s, 1H), piperidin-4- 4.97-4.53 (m, 2H), 4.43-4.31 (m, 2H), 4.30-4.13 yl]phenyl}azetidine- (m, 2H), 3.78-3.56 (m, 1H), 2.85-2.65 (m, 3-carboxamide 2H), 1.81-1.63 (m, 2H), 1.59-1.42 (m, 2H), 1.33 (s, 6H) 20 N-{4-[1-(2- ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.01 (s, (ESI(+)) hydroxy-2- 1H), 7.93 (dd, J = 4.6, 1.3 Hz, 1H), 7.85 (d, m/e 423 methylpropanoyl) J = 2.8 Hz, 1H), 7.57-7.49 (m, 2H), 7.26-7.09 (m, (M + H)⁺ piperidin-4- 3H), 6.86 (ddd, J = 8.2, 2.9, 1.4 Hz, 1H), 5.37 (s, yl]phenyl}-1- 1H), 4.77 (bs, 1H), 4.09 (t, J = 7.8 Hz, 2H), 3.95 (pyridin-3- (t, J = 6.6 Hz, 2H), 3.77-3.55 (m, 1H), yl)azetidine-3- 3.18-2.62 (m, 2H), 1.81-1.71 (m, 2H), 1.67-1.35 carboxamide (m, 2H), 1.33 (s, 6H), 1.30-1.00 (m, 1H) 22 N-(4-{1-[(2S)-2- ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.01 (s, (ESI(+)) methylbutanoyl] 1H), 7.93 (dd, J = 4.6, 1.4 Hz, 1H), 7.86 (d, m/e 421 piperidin-4- J = 2.8 Hz, 1H), 7.57-7.49 (m, 2H), 7.25-7.09 (m, (M + H)⁺ yl}phenyl)-1- 3H), 6.90-6.82 (m, 1H), 4.63-4.52 (m, 1H), (pyridin-3- 4.18-3.87 (m, 5H), 3.78-3.63 (m, 1H), yl)azetidine-3- 3.16-2.99 (m, 1H), 2.81-2.67 (m, 2H), 2.59 (d, carboxamide J = 12.4 Hz, 1H), 1.88-1.67 (m, 2H), 1.68-1.07 (m, 4H), 1.05-0.94 (m, 3H), 0.91-0.72 (m, 3H) 25 1-(pyridin-3-yl)- ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.01 (s, (ESI(+)) N-{4-[1- 1H), 7.93 (dd, J = 4.6, 1.3 Hz, 1H), 7.85 (d, m/e 463 (tetrahydro-2H- J = 2.8 Hz, 1H), 7.57-7.49 (m, 2H), 7.22-7.14 (m, (M + H)⁺ pyran-4-ylacetyl) 3H), 6.86 (ddd, J = 8.2, 2.8, 1.4 Hz, 1H), piperidin-4- 4.60-4.49 (m, 1H), 4.09 (t, J = 7.8 Hz, 2H), 3.97 (dd, yl]phenyl}azetidine- J = 16.6, 10.2 Hz, 2H), 3.88-3.62 (m, 3H), 3-carboxamide 3.14-3.00 (m, 1H), 2.77-2.65 (m, 1H), 2.57 (t, J = 11.1 Hz, 1H), 2.27 (d, J = 6.8 Hz, 2H), 1.91 (dd, J = 9.4, 5.6 Hz, 1H), 1.74 (d, J = 11.3 Hz, 3H), 1.59 (d, J = 12.9 Hz, 2H), 1.43 (dd, J = 31.3, 12.2 Hz, 3H), 1.20 (dd, J = 24.5, 12.0 Hz, 3H) 26 N-[4-(1- ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.01 (s, (ESI(+)) benzoylpiperidin- 1H), 7.93 (dd, J = 4.7, 1.3 Hz, 1H), 7.86 (d, m/e 441 4-yl)phenyl]-1- J = 2.7 Hz, 1H), 7.54 (d, J = 8.5 Hz, 2H), 7.48-7.36 (M + H)⁺ (pyridin-3- (m, 5H), 7.27-7.11 (m, 3H), 6.86 (ddd, J = 8.3, yl)azetidine-3- 2.8, 1.3 Hz, 1H), 4.62 (s, 1H), 4.13-4.01 (m, carboxamide 2H), 3.97 (dd, J = 12.1, 5.8 Hz, 2H), 3.71 (ddd, J = 14.3, 8.1, 6.1 Hz, 2H), 3.13 (s, 1H), 2.76 (t, J = 11.7 Hz, 2H), 1.85 (d, J = 32.6 Hz, 2H), 1.66-1.40 (m, 2H) 29 N-{4-[1-(2- ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.00 (s, (ESI(+)) methylpropanoyl) 1H), 7.88 (dd, J = 4.7, 1.4 Hz, 1H), 7.57-7.49 m/e 421 piperidin-4- (m, 2H), 7.22-7.14 (m, 2H), 7.07 (dd, J = 8.0, (M + H)⁺ yl]phenyl}-1-(2- 4.7 Hz, 1H), 6.85 (dd, J = 8.1, 1.4 Hz, 1H), methylpyridin-3- 4.60-4.49 (m, 1H), 4.15-3.85 (m, 4H), 3.68-3.53 yl)azetidine-3- (m, 1H), 3.21-3.02 (m, 1H), 2.97-2.61 (m, carboxamide 2H), 2.35 (s, 3H), 2.32-1.66 (m, 3H), 1.60-1.14 (m, 3H), 1.12-0.92 (m, 6H) 30 N-{4-[1-(2- ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.01 (s, (ESI(+)) methylpropanoyl) 1H), 8.11-7.82 (m, 2H), 7.80-7.31 (m, 2H), m/e 407 piperidin-4- 7.33-7.07 (m, 2H), 6.86 (ddd, J = 8.3, 2.9, 1.4 (M + H)⁺ yl]phenyl}-1- Hz, 1H), 4.61-4.49 (m, 1H), 4.16-3.87 (m, (pyridin-3- 4H), 3.77-3.64 (m, 1H), 3.20-2.99 (m, 1H), yl)azetidine-3- 2.89 (p, J = 6.7 Hz, 1H), 2.80-2.61 (m, 1H), carboxamide 2.64-2.47 (m, 1H), 1.89-1.60 (m, 2H), 1.61-1.30 (m, 2H), 1.08 (d, J = 6.8 Hz, 2H), 1.05-0.97 (m, 6H) 71 N-{4-[1-(2- ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.00 (s, (ESI(+)) hydroxy-2- 1H), 7.88 (dd, J = 4.7, 1.4 Hz, 1H), 7.57-7.50 m/e 437 methylpropanoyl) (m, 2H), 7.21-7.14 (m, 2H), 7.07 (dd, J = 8.0, (M + H)⁺ piperidin-4- 4.6 Hz, 1H), 6.85 (dd, J = 8.1, 1.4 Hz, 1H), 5.37 yl]phenyl}-1-(2- (s, 1H), 4.65 (bs, 1H), 4.10 (t, J = 7.7 Hz, 2H), methylpyridin-3- 3.97 (t, J = 6.8 Hz, 2H), 3.70-3.56 (m, 1H), yl)azetidine-3- 3.05-2.63 (m, 2H), 2.35 (s, 3H), 1.81-1.71 carboxamide (m, 2H), 1.66-1.36 (m, 3H), 1.33 (s, 6H), 128-1.13 (m, 1H) 72 N-{4-[1-(2- ¹H NMR (300 MHz, DMSO-d₆) δ ppm 9.99 (s, (ESI(+)) hydroxy-2- 1H), 7.90 (d, J = 4.7 Hz, 1H), 7.76 (s, 1H), m/e 437 methylpropanoyl) 7.57-7.50 (m, 2H), 7.21-7.14 (m, 2H), 7.00 (d, (M + H)⁺ piperidin-4- J = 4.7 Hz, 1H), 5.35 (s, 1H), 4.71 (bs, 2H), 4.15 (t, yl]phenyl}-1-(4- J = 7.7 Hz, 2H), 4.05 (t, J = 6.8 Hz, 2H), methylpyridin-3- 3.72-3.58 (m, 1H), 3.22-2.63 (m, 1H), 2.18 (s, 3H), yl)azetidine-3- 1.82-1.72 (m, 2H), 1.62-1.36 (m, 2H), 1.33 carboxamide (s, 6H), 1.20 (d, J = 18.3 Hz, 1H), 0.89-0.72 (m, 1H) 73 N-{4-[1-(2- ¹H NMR (300 MHz, DMSO-d₆) δ ppm 9.94 (s, (ESI(+)) hydroxy-2- 1H), 7.56-7.49 (m, 3H), 7.21-7.13 (m, 2H), m/e 453 methylpropanoyl) 6.84 (dd, J = 7.5, 4.9 Hz, 1H), 6.72 (dd, J = 7.5, (M + H)⁺ piperidin-4- 1.6 Hz, 1H), 5.35 (s, 1H), 4.72 (bs, 2H), 4.07 (t, yl]phenyl}-1-(2- J = 7.9 Hz, 2H), 3.95 (d, J = 6.9 Hz, 2H), 3.83 (s, methoxypyridin- 3H), 3.66-3.52 (m, 1H), 2.73 (t, J = 11.9 Hz, 3-yl)azetidine-3- 2H), 1.82-1.71 (m, 2H), 1.59-1.36 (m, 2H), carboxamide 1.33 (s, 6H) 96 N-{4-[1-(2- ¹H NMR (300 MHz, DMSO-d₆) δ ppm 9.94 (s, (ESI(+)) hydroxy-2- 1H), 7.93 (d, J = 5.3 Hz, 1H), 7.63 (s, 1H), m/e 453 methylpropanoyl) 7.56-7.49 (m, 2H), 7.21-7.13 (m, 2H), 6.88 (d, (M + H)⁺ piperidin-4- J = 5.4 Hz, 1H), 5.35 (s, 1H), 4.71 (bs, 1H), 4.09 (t, yl]phenyl}-1-(4- J = 7.9 Hz, 2H), 3.96 (dd, J = 12.1, 4.8 Hz, 2H), methoxypyridin- 3.79 (s, 3H), 3.71-3.54 (m, 2H), 2.73 (t, J = 11.8 3-yl)azetidine-3- Hz, 1H), 1.76 (d, J = 11.4 Hz, 3H), 1.51 (s, carboxamide 3H), 1.33 (s, 6H) 97 1-(4-cyanopyridin-3- ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.04 (s, (ESI(+)) yl)-N-{4-[1-(2- 1H), 8.09 (s, 1H), 7.96 (d, J = 5.0 Hz, 1H), 7.54 m/e 448 hydroxy-2- (d, J = 8.6 Hz, 2H), 7.46 (dd, J = 5.1, 0.5 Hz, (M + H)⁺ methylpropanoyl) 1H), 7.18 (d, J = 8.6 Hz, 2H), 5.36 (s, 1H), 4.74 piperidin-4- (s, 1H), 4.43 (t, J = 8.3 Hz, 2H), 4.31 (dd, yl]phenyl}azetidine- J = 8.0, 5.8 Hz, 2H), 3.79-3.66 (m, 1H), 2.74 (dd, 3-carboxamide J = 13.8, 10.3 Hz, 2H), 1.81-1.72 (m, 3H), 1.65-1.45 (m, 3H), 1.33 (s, 6H) 98 N-[4-(1- (ESI(+)) pentanoylpiperidin- m/e 421 4-yl)phenyl]-1- (M + H)⁺ (pyridin-3- yl)azetidine-3- carboxamide 99 N-{4-[1-(3- (ESI(+)) methylpentanoyl) m/e 435 piperidin-4- (M + H)⁺ yl]phenyl}-1- (pyridin-3- yl)azetidine-3- carboxamide 100 N-(4-{1-[(1S,4R)- (ESI(+)) bicyclo[2.2.1]hept-2- m/e 473 ylacetyl]piperidin- (M + H)⁺ 4-yl}phenyl)-1- (pyridin-3- yl)azetidine-3- carboxamide 101 N-{4-[1- (ESI(+)) (cyclopentylacetyl) m/e 447 piperidin-4- (M + H)⁺ yl]phenyl}-1- (pyridin-3- yl)azetidine-3- carboxamide 102 N-(4-{1-[(2- (ESI(+)) methylcyclopropyl) m/e 419 carbonyl]piperidin- (M + H)⁺ 4-yl}phenyl)-1- (pyridin-3- yl)azetidine-3- carboxamide 103 N-{4-[1- (ESI(+)) (morpholin-4- m/e 464 ylacetyl)piperidin- (M + H)⁺ 4-yl]phenyl}-1- (pyridin-3- yl)azetidine-3- carboxamide 104 N-{4-[1-(furan-3- (ESI(+)) ylcarbonyl)piperidin- m/e 431 4-yl]phenyl}- (M + H)⁺ 1-(pyridin-3- yl)azetidine-3- carboxamide 105 1-(pyridin-3-yl)- (ESI(+)) N-{4-[1-(pyrrolidin-1- m/e 474 ylacetyl)piperidin-4- (M + H)⁺ yl]phenyl}azetidine- 3-carboxamide 106 N-{4-[1-(5-oxo-D- (ESI(+)) prolyl)piperidin- m/e 448 4-yl]phenyl}-1- (M + H)⁺ (pyridin-3- yl)azetidine-3- carboxamide 107 N-{4-[1-(N,N- (ESI(+)) dimethyl-beta- m/e 436 alanyl)piperidin- (M + H)⁺ 4-yl]phenyl}-1- (pyridin-3- yl)azetidine-3- carboxamide 108 1-(pyridin-3-yl)- (ESI(+)) N-{4-[1-(1,3- m/e 448 thiazol-2-ylcarbonyl) (M + H)⁺ piperidin-4- yl]phenyl}azetidine- 3-carboxamide 109 1-(pyridin-3-yl)- (ESI(+)) N-{4-[1- m/e 447 (thiophen-3- (M + H)⁺ ylcarbonyl) piperidin-4- yl]phenyl}azetidine- 3-carboxamide 110 N-(4-{1-[(1- (ESI(+)) methylcyclopropyl) m/e 419 carbonyl]piperidin- (M + H)⁺ 4-yl}phenyl)-1- (pyridin-3- yl)azetidine-3- carboxamide 111 N-(4-{1-[(3- (ESI(+)) methylthiophen- m/e 461 2-yl)carbonyl] (M + H)⁺ piperidin-4- yl}phenyl)-1- (pyridin-3- yl)azetidine-3- carboxamide 112 1-(pyridin-3-yl)- (ESI(+)) N-{4-[1-(4,4,4- m/e 461 trifluorobutanoyl) (M + H)⁺ piperidin-4- yl]phenyl}azetidine- 3-carboxamide 113 N-(4-{1-[(4- (ESI(+)) methylpiperazin-1- m/e 477 yl)acetyl]piperidin- (M + H)⁺ 4-yl}phenyl)-1- (pyridin-3- yl)azetidine-3- carboxamide 114 N-{4-[1-(5-oxo-L- (ESI(+)) prolyl)piperidin- m/e 448 4-yl]phenyl}-1- (M + H)⁺ (pyridin-3- yl)azetidine-3- carboxamide 115 N-{4-[1-(3- (ESI(+)) ethoxypropanoyl) m/e 437 piperidin-4- (M + H)⁺ yl]phenyl}-1- (pyridin-3- yl)azetidine-3- carboxamide 116 N-{4-[1-(4- (ESI(+)) methylpentanoyl) m/e 435 piperidin-4- (M + H)⁺ yl]phenyl}-1- (pyridin-3- yl)azetidine-3- carboxamide 117 N-(4-{1-[(1- (ESI(+)) methylcyclohexyl) m/e 461 carbonyl]piperidin- (M + H)⁺ 4-yl}phenyl)- 1-(pyridin-3- yl)azetidine-3- carboxamide 118 N-[4-(1- (ESI(+)) acetylpiperidin- m/e 379 4-yl)phenyl]-1- (M + H)⁺ (pyridin-3- yl)azetidine-3- carboxamide 119 N-{4-[1- (ESI(+)) (cyclohexylacetyl) m/e 461 piperidin-4- (M + H)⁺ yl]phenyl}-1- (pyridin-3- yl)azetidine-3- carboxamide 120 N-{4-[1-(N- (ESI(+)) acetyl-L- m/e 492 leucyl)piperidin- (M + H)⁺ 4-yl]phenyl}-1- (pyridin-3- yl)azetidine-3- carboxamide 121 N-[4-(1- (ESI(+)) propanoylpiperidin- m/e 393 4-yl)phenyl]- (M + H)⁺ 1-(pyridin-3- yl)azetidine-3- carboxamide 122 1-(pyridin-3-yl)- (ESI(+)) N-{4-[1-(3,3,3- m/e 447 trifluoropropanoyl) (M + H)⁺ piperidin-4- yl]phenyl}azetidine- 3-carboxamide 123 N-(4-{1-[(2- (ESI(+)) methoxyethoxy) m/e 453 acetyl]piperidin-4- (M + H)⁺ yl}phenyl)-1- (pyridin-3- yl)azetidine-3- carboxamide 124 N-(4-{1-[3- (ESI(+)) (morpholin-4- m/e 478 yl)propanoyl] (M + H)⁺ piperidin-4- yl}phenyl)-1- (pyridin-3- yl)azetidine-3- carboxamide 125 N-{4-[1-(2,2- (ESI(+)) dimethylpropanoyl) m/e 421 piperidin-4- (M + H)⁺ yl]phenyl}-1- (pyridin-3- yl)azetidine-3- carboxamide 126 N-(4-{1-[(5- (ESI(+)) methylthiophen-2- m/e 461 yl)carbonyl]piperidin- (M + H)⁺ 4-yl}phenyl)-1- (pyridin-3- yl)azetidine-3- carboxamide 127 1-(pyridin-3-yl)- (ESI(+)) N-{4-[1- m/e 447 (thiophen-2- (M + H)⁺ ylcarbonyl)piperidin- 4-yl]phenyl}azetidine- 3-carboxamide 128 N-(4-{1-[(1- (ESI(+)) methyl-1H- m/e 444 pyrrol-2- (M + H)⁺ yl)carbonyl]piperidin- 4-yl}phenyl)-1- (pyridin-3- yl)azetidine-3- carboxamide 129 N-{4-[1-(furan-2- (ESI(+)) ylcarbonyl)piperidin- m/e 431 4-yl]phenyl}- (M + H)⁺ 1-(pyridin-3- yl)azetidine-3- carboxamide 130 N-(4-{1-[3- (ESI(+)) (piperidin-1- m/e 476 yl)propanoyl] (M + H)⁺ piperidin-4- yl}phenyl)-1- (pyridin-3- yl)azetidine-3- carboxamide 131 N-{4-[1- (ESI(+)) (ethoxyacetyl) m/e 423 piperidin-4- (M + H)⁺ yl]phenyl}-1- (pyridin-3- yl)azetidine-3- carboxamide 132 N-{4-[1-(3,3- (ESI(+)) dimethylbutanoyl) m/e 435 piperidin-4- (M + H)⁺ yl]phenyl}-1- (pyridin-3- yl)azetidine-3- carboxamide 133 N-{4-[1-(2,2- (ESI(+)) dimethylbutanoyl) m/e 435 piperidin-4- (M + H)⁺ yl]phenyl}-1- (pyridin-3- yl)azetidine-3- carboxamide 134 N-[4-(1- (ESI(+)) butanoylpiperidin- m/e 407 4-yl)phenyl]-1- (M + H)⁺ (pyridin-3- yl)azetidine-3- carboxamide 135 N-{4-[1- (ESI(+)) (methoxyacetyl) m/e 409 piperidin-4- (M + H)⁺ yl]phenyl}-1- (pyridin-3- yl)azetidine-3- carboxamide 136 N-{4-[1- (ESI(+)) (cyclohexylcarbonyl) m/e 447 piperidin-4- (M + H)⁺ yl]phenyl}-1- (pyridin-3- yl)azetidine-3- carboxamide 137 N-{4-[1-(3- (ESI(+)) methylbutanoyl) m/e 421 piperidin-4- (M + H)⁺ yl]phenyl}-1- (pyridin-3- yl)azetidine-3- carboxamide 138 N-{4-[1- (ESI(+)) (cyclopentylcarbonyl) m/e 433 piperidin-4- (M + H)⁺ yl]phenyl}-1- (pyridin-3- yl)azetidine-3- carboxamide 139 N-{4-[1-(2,3- (ESI(+)) dimethylbutanoyl) m/e 435 piperidin-4- (M + H)⁺ yl]phenyl}-1- (pyridin-3- yl)azetidine-3- carboxamide 149 N-[4-(1- (ESI(+)) benzoylpiperidin- m/e 455 4-yl)phenyl]-1-(2- (M + H)⁺ methylpyridin-3- yl)azetidine-3- carboxamide 150 N-{4-[1-(2- (ESI(+)) fluorobenzoyl) m/e 473 piperidin-4- (M + H)⁺ yl]phenyl}-1-(2- methylpyridin-3- yl)azetidine-3- carboxamide 151 N-{4-[1-(2- (ESI(+)) chlorobenzoyl) m/e 489 piperidin-4- (M + H)⁺ yl]phenyl}-1-(2- methylpyridin-3- yl)azetidine-3- carboxamide 152 N-{4-[1-(3- (ESI(+)) fluorobenzoyl) m/e 473 piperidin-4- (M + H)⁺ yl]phenyl}-1-(2- methylpyridin-3- yl)azetidine-3- carboxamide 153 N-{4-[1-(3- (ESI(+)) chlorobenzoyl) m/e 489 piperidin-4- (M + H)⁺ yl]phenyl}-1-(2- methylpyridin-3- yl)azetidine-3- carboxamide 154 N-{4-[1-(3,5- (ESI(+)) dichlorobenzoyl) m/e 523 piperidin-4- (M + H)⁺ yl]phenyl}-1-(2- methylpyridin-3- yl)azetidine-3- carboxamide 155 N-{4-[1-(4- (ESI(+)) fluorobenzoyl) m/e 473 piperidin-4- (M + H)⁺ yl]phenyl}-1-(2- methylpyridin-3- yl)azetidine-3- carboxamide 156 N-{4-[1-(4- (ESI(+)) chlorobenzoyl) m/e 489 piperidin-4- (M + H)⁺ yl]phenyl}-1-(2- methylpyridin-3- yl)azetidine-3- carboxamide 157 1-(2-methylpyridin-3- (ESI(+)) yl)-N-(4-{1-[4- m/e 523 (trifluoromethyl) (M + H)⁺ benzoyl]piperidin-4- yl}phenyl)azetidine- 3-carboxamide 158 1-(2-methylpyridin-3- (ESI(+)) yl)-N-{4-[1- m/e 457 (pyridazin-3- (M + H)⁺ ylcarbonyl)piperidin- 4-yl]phenyl}azetidine- 3-carboxamide 159 1-(2-methylpyridin-3- (ESI(+)) yl)-N-[4-(1- m/e 435 pentanoylpiperidin- (M + H)⁺ 4-yl)phenyl]azetidine- 3-carboxamide 160 N-{4-[1-(3- (ESI(+)) methylpentanoyl) m/e 449 piperidin-4- (M + H)⁺ yl]phenyl}-1-(2- methylpyridin-3- yl)azetidine-3- carboxamide 161 N-(4-{1-[(1S,4R)- (ESI(+)) bicyclo[2.2.1]hept-2- m/e 487 ylacetyl]piperidin- (M + H)⁺ 4-yl}phenyl)-1- (2-methylpyridin-3- yl)azetidine-3- carboxamide 162 N-{4-[1- (ESI(+)) (cyclopentylacetyl) m/e 461 piperidin-4- (M + H)⁺ yl]phenyl}-1-(2- methylpyridin-3- yl)azetidine-3- carboxamide 163 N-(4-{1-[(2- (ESI(+)) methylcyclopropyl) m/e 433 carbonyl]piperidin- (M + H)⁺ 4-yl}phenyl)-1-(2- methylpyridin-3- yl)azetidine-3- carboxamide 164 1-(2-methylpyridin-3- (ESI(+)) yl)-N-{4-[1- m/e 478 (morpholin-4- (M + H)⁺ ylacetyl)piperidin- 4-yl]phenyl}azetidine- 3-carboxamide 165 N-{4-[1-(furan-3- (ESI(+)) ylcarbonyl)piperidin- m/e 445 4-yl]phenyl}- (M + H)⁺ 1-(2-methylpyridin-3- yl)azetidine-3- carboxamide 166 1-(2-methylpyridin-3- (ESI(+)) yl)-N-{4-[1- m/e 462 (pyrrolidin-1- (M + H)⁺ ylacetyl)piperidin- 4-yl]phenyl}azetidine- 3-carboxamide 167 1-(2- (ESI(+)) methylpyridin-3- m/e 462 yl)-N-{4-[1-(5- (M + H)⁺ oxo−D-prolyl) piperidin-4- yl]phenyl}azetidine- 3-carboxamide 168 N-{4-[1-(N,N- (ESI(+)) dimethyl-beta- m/e 450 alanyl)piperidin- (M + H)⁺ 4-yl]phenyl}-1- (2-methylpyridin-3- yl)azetidine-3- carboxamide 169 1-(2-methylpyridin-3- (ESI(+)) yl)-N-{4-[1- m/e 461 (thiophen-3- (M + H)⁺ ylcarbonyl)piperidin- 4-yl]phenyl}azetidine- 3-carboxamide 170 N-(4-{1-[(1- (ESI(+)) methylcyclopropyl) m/e 433 carbonyl]piperidin- (M + H)⁺ 4-yl}phenyl)-1-(2- methylpyridin-3- yl)azetidine-3- carboxamide 171 1-(2-methylpyridin-3- (ESI(+)) yl)-N-(4-{1-[(3- m/e 475 methylthiophen-2- (M + H)⁺ yl)carbonyl]piperidin- 4-yl}phenyl)azetidine- 3-carboxamide 172 1-(2-methylpyridin-3- (ESI(+)) yl)-N-{4-[1-(4,4,4- m/e 475 trifluorobutanoyl) (M + H)⁺ piperidin-4- yl]phenyl}azetidine- 3-carboxamide 173 N-(4-{1-[(4- (ESI(+)) methylpiperazin-1- m/e 491 yl)acetyl]piperidin- (M + H)⁺ 4-yl}phenyl)-1-(2- methylpyridin-3- yl)azetidine-3- carboxamide 174 1-(2-methylpyridin-3- (ESI(+)) yl)-N-{4-[1-(5-oxo-L- m/e 462 prolyl)piperidin-4- (M + H)⁺ yl]phenyl}azetidine- 3-carboxamide 175 N-{4-[1-(3- (ESI(+)) ethoxypropanoyl) m/e 451 piperidin-4- (M + H)⁺ yl]phenyl}-1-(2- methylpyridin-3- yl)azetidine-3- carboxamide 176 N-{4-[1-(4- (ESI(+)) methylpentanoyl) m/e 449 piperidin-4- (M + H)⁺ yl]phenyl}-1-(2- methylpyridin-3- yl)azetidine-3- carboxamide 177 N-(4-{1-[(1- (ESI(+)) methylcyclohexyl) m/e 475 carbonyl]piperidin- (M + H)⁺ 4-yl}phenyl)- 1-(2-methylpyridin-3- yl)azetidine-3- carboxamide 178 N-[4-(1- (ESI(+)) acetylpiperidin- m/e 393 4-yl)phenyl]-1-(2- (M + H)⁺ methylpyridin-3- yl)azetidine-3- carboxamide 179 N-{4-[1- (ESI(+)) (cyclohexylacetyl) m/e 475 piperidin-4- (M + H)⁺ yl]phenyl}-1-(2- methylpyridin-3- yl)azetidine-3- carboxamide 180 N-{4-[1-(N- (ESI(+)) acetyl-L- m/e 506 leucyl)piperidin- (M + H)⁺ 4-yl]phenyl}-1-(2- methylpyridin-3- yl)azetidine-3- carboxamide 181 1-(2-methylpyridin-3- (ESI(+)) yl)-N-[4-(1- m/e 407 propanoylpiperidin- (M + H)⁺ 4-yl)phenyl]azetidine- 3-carboxamide 182 1-(2-methylpyridin-3- (ESI(+)) yl)-N-{4-[1-(3,3,3- m/e 461 trifluoropropanoyl) (M + H)⁺ piperidin-4- yl]phenyl}azetidine- 3-carboxamide 183 N-(4-{1-[(2- (ESI(+)) methoxyethoxy) m/e 467 acetyl]piperidin-4- (M + H)⁺ yl}phenyl)-1-(2- methylpyridin-3- yl)azetidine-3- carboxamide 184 1-(2-methylpyridin-3- (ESI(+)) yl)-N-(4-{1-[3- m/e 492 (morpholin-4- (M + H)⁺ yl)propanoyl] piperidin-4- yl}phenyl)azetidine- 3-carboxamide 185 N-{4-[1-(2,2- (ESI(+)) dimethylpropanoyl) m/e 435 piperidin-4- (M + H)⁺ yl]phenyl}-1-(2- methylpyridin-3- yl)azetidine-3- carboxamide 186 1-(2-methylpyridin-3- (ESI(+)) yl)-N-(4-{1-[(5- m/e 475 methylthiophen-2- (M + H)⁺ yl)carbonyl] piperidin-4- yl}phenyl)azetidine- 3-carboxamide 187 1-(2-methylpyridin-3- (ESI(+)) yl)-N-{4-[1- m/e 461 (thiophen-2- (M + H)⁺ ylcarbonyl) piperidin-4- yl]phenyl}azetidine- 3-carboxamide 188 1-(2-methylpyridin-3- (ESI(+)) yl)-N-(4-{1-[(1- m/e 458 methyl-1H- (M + H)⁺ pyrrol-2- yl)carbonyl] piperidin-4- yl}phenyl)azetidine- 3-carboxamide 189 N-{4-[1-(furan-2- (ESI(+)) ylcarbonyl) m/e 445 piperidin-4-yl] (M + H)⁺ phenyl}-1-(2- methylpyridin-3- yl)azetidine-3- carboxamide 190 1-(2-methylpyridin-3- (ESI(+)) yl)-N-(4-{1-[3- m/e 490 (piperidin-1- (M + H)⁺ yl)propanoyl] piperidin-4- yl}phenyl)azetidine- 3-carboxamide 191 N-{4-[1- (ESI(+)) (ethoxyacetyl) m/e 437 piperidin-4- (M + H)⁺ yl]phenyl}-1-(2- methylpyridin-3- yl)azetidine-3- carboxamide 192 N-{4-[1-(3,3- (ESI(+)) dimethylbutanoyl) m/e 449 piperidin-4- (M + H)⁺ yl]phenyl}-1-(2- methylpyridin-3- yl)azetidine-3- carboxamide 193 N-{4-[1-(2,2- (ESI(+)) dimethylbutanoyl) m/e 449 piperidin-4- (M + H)⁺ yl]phenyl}-1-(2- methylpyridin-3- yl)azetidine-3- carboxamide 194 N-[4-(1- (ESI(+)) butanoylpiperidin- m/e 421 4-yl)phenyl]-1- (M + H)⁺ (2-methylpyridin-3- yl)azetidine-3- carboxamide 195 N-{4-[1- (ESI(+)) (methoxyacetyl) m/e 423 piperidin-4- (M + H)⁺ yl]phenyl}-1-(2- methylpyridin-3- yl)azetidine-3- carboxamide 196 N-{4-[1- (ESI(+)) (cyclohexylcarbonyl) m/e 461 piperidin-4- (M + H)⁺ yl]phenyl}-1-(2- methylpyridin-3- yl)azetidine-3- carboxamide 197 N-{4-[1-(3- (ESI(+)) methylbutanoyl) m/e 435 piperidin-4- (M + H)⁺ yl]phenyl}-1-(2- methylpyridin-3- yl)azetidine-3- carboxamide 198 N-{4-[1-(2,3- (ESI(+)) dimethylbutanoyl) m/e 449 piperidin-4- (M + H)⁺ yl]phenyl}-1-(2- methylpyridin-3- yl)azetidine-3- carboxamide

Example 11 (3S)-1-(pyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1D-E, substituting tert-butyl 4-[4-({[(3S)-1-(pyridin-3-yl)pyrrolidin-3-yl]carbonyl}amino)phenoxy]piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate in Example 1D. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 9.98 (s, 1H), 7.99 (d, J=2.9 Hz, 1H), 7.91 (d, J=4.8 Hz, 1H), 7.50 (s, 2H), 7.33 (dd, J=8.5, 4.8 Hz, 1H), 7.16-7.09 (m, 1H), 6.97-6.89 (m, 2H), 4.58-4.47 (m, 1H), 3.95-3.65 (m, 4H), 3.56 (d, J=8.6 Hz, 1H), 3.50-3.32 (m, 6H), 2.36-2.11 (m, 4H), 2.01-1.79 (m, 3H), 1.66-1.38 (m, 4H), 1.32-1.08 (m, 3H); MS (ESI(+)) m/e 493 (M+H)⁺.

The following Examples were prepared essentially as described in Example 1D-E, substituting tert-butyl 4-[4-({[(3S)-1-(pyridin-3-yl)pyrrolidin-3-yl] carbonyl}amino)phenoxy]piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl) azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate in Example 1D and the appropriate carboxylic acid for 2-(tetrahydro-2H-pyran-4-yl)acetic acid in Example 1E. Some products were purified by flash chromatography while others were purified by reverse-phase HPLC. Accordingly, some Examples were isolated as trifluoroacetic acid salts.

TABLE 3 Ex Name ¹H NMR MS 12 (3S)-N-(4-{[1-(2- ¹H NMR (300 MHz, DMSO-d₆) δ ppm 9.97 (s, (ESI(+)) methylpropanoyl) 1H), 7.96 (d, J = 2.9 Hz, 1H), 7.86 (dd, J = 4.6, m/e 437 piperidin-4- 1.3 Hz, 1H), 7.55 -7.48 (m, 2H), 7.19 (dd, (M + H)⁺ yl]oxy}phenyl)- J = 8.4, 4.6 Hz, 1H), 6.99-6.90 (m, 3H), 1-(pyridin-3- 4.59-4.48 (m, 1H), 4.03-3.67 (m, 3H), 3.54 (d, yl)pyrrolidine-3- J = 8.6 Hz, 1H), 3.47-3.38 (m, 2H), 3.35 (d, J = 7.4 carboxamide Hz, 2H), 3.28-3.18 (m, 1H), 2.95-2.82 (m, 1H), 2.38-2.03 (m, 2H), 2.00-1.80 (m, 2H), 1.64-1.37 (m, 2H), 1.00 (d, J = 6.7 Hz, 6H) 13 (3S)-1-(pyridin- ¹H NMR (300 MHz, DMSO-d₆) δ ppm 9.97 (s, (ESI(+)) 3-yl)-N-[4-({1- 1H), 7.97 (d, J = 2.8 Hz, 1H), 7.88 (d, J = 5.1 m/e 465 [(2S)- Hz, 1H), 7.55-7.48 (m, 2H), 7.33-7.19 (m, (M + H)⁺ tetrahydrofuran- 1H), 7.05-6.88 (m, 3H), 4.67 (t, J = 6.5 Hz, 2-ylcarbonyl] 1H), 4.57-4.50 (m, 1H), 3.94-3.67 (m, 4H), piperidin-4- 3.55 (d, J = 8.6 Hz, 1H), 3.47-3.38 (m, 4H), yl}oxy)phenyl] 2.38-2.12 (m, 2H), 2.07-1.74 (m, 7H), pyrrolidine-3- 1.65-1.00 (m, 3H) carboxamide 14 (3S)-1-(pyridin- ¹H NMR (300 MHz, DMSO-d₆) δ ppm 9.97 (s, (ESI(+)) 3-yl)-N-[4-({1- 1H), 7.96 (d, J = 2.9 Hz, 1H), 7.87 (dd, J = 4.6, m/e 465 [(2R)- 1.2 Hz, 1H), 7.55-7.48 (m, 2H), 7.21 (dd, (M + H)⁺ tetrahydrofuran- J = 8.4, 4.6 Hz, 1H), 7.02-6.93 (m, 2H), 6.92 (s, 2-ylcarbonyl] 1H), 4.67 (t, J = 6.6 Hz, 1H), 4.57-4.50 (m, piperidin-4- 1H), 3.94-3.62 (m, 4H), 3.54 (d, J = 8.6 Hz, yl}oxy)phenyl] 1H), 3.44 (d, J = 6.7 Hz, 2H), 3.41 (d, J = 5.4 pyrrolidine-3- Hz, 2H), 3.23 (d, J = 7.8 Hz, 1H), 2.36-2.07 carboxamide (m, 3H), 2.09-1.76 (m, 6H), 1.65-1.39 (m, 2H) 15 (3S)-1-(pyridin- ¹H NMR (300 MHz, DMSO-d₆) δ ppm 9.97 (s, (ESI(+)) 3-yl)-N-(4-{[1- 1H), 7.97 (d, J = 2.9 Hz, 1H), 7.88 (dd, J = 4.7, m/e 465 (tetrahydrofuran- 1.2 Hz, 1H), 7.55-7.48 (m, 2H), 7.25 (dd, (M + H)⁺ 3-ylcarbonyl) J = 8.4, 4.7 Hz, 1H), 7.02 (dd, J = 8.5, 2.8 Hz, 1H), piperidin-4- 6.97-6.90 (m, 2H), 4.60-4.48 (m, 1H), 3.98-3.61 yl]oxy}phenyl) (m, 7H), 3.55 (d, J = 8.6 Hz, 1H), 3.45 (d, pyrrolidine-3- J = 6.9 Hz, 2H), 3.44-3.39 (m, 2H), 3.38-3.32 carboxamide (m, 2H), 2.38-2.09 (m, 2H), 2.10-1.81 (m, 4H), 1.65-1.40 (m, 2H) 16 (3S)-N-(4-{[1- ¹H NMR (300 MHz, DMSO-d₆) δ ppm 9.96 (s, (ESI(+)) (cyclopropylacetyl) 1H), 7.99-7.93 (m, 1H), 7.85 (dd, J = 4.6, 1.3 m/e 449 piperidin-4- Hz, 1H), 7.55-7.48 (m, 2H), 7.16 (dd, J = 8.4, (M + H)⁺ yl]oxy}phenyl)- 4.5 Hz, 1H), 6.98-6.87 (m, 3H), 4.59-4.47 (m, 1-(pyridin-3- 1H), 3.92-3.80 (m, 1H), 3.73-3.61 (m, 1H), yl)pyrrolidine-3- 3.54 (d, J = 8.6 Hz, 1H), 3.47-3.37 (m, 2H), carboxamide 3.26-3.07 (m, 3H), 2.27 (d, J = 6.8 Hz, 3H), 2.23-2.12 (m, 1H), 1.97-1.79 (m, 2H), 1.62-1.32 (m, 2H), 1.04-0.83 (m, 1H), 0.49-0.36 (m, 2H), 0.19-0.07 (m, 2H) 17 (3S)-N-(4-{[1-(2- ¹H NMR (300 MHz, DMSO-d₆) δ ppm 9.96 (s, (ESI(+)) hydroxy-2- 1H), 7.96 (d, J = 3.1 Hz, 1H), 7.87 (d, J = 4.7 m/e 453 methylpropanoyl) Hz, 1H), 7.57-7.39 (m, 2H), 7.21 (dd, J = 8.4, (M + H)⁺ piperidin-4- 4.6 Hz, 1H), 7.03-6.88 (m, 3H), 5.38 (s, 1H), yl]oxy}phenyl)- 4.59-3.79 (m, 3H), 3.65-3.38 (m, 4H), 1-(pyridin-3- 2.35-2.10 (m, 2H), 1.99-1.84 (m, 2H), 1.63-1.34 yl)pyrrolidine-3- (m, 3H), 1.35-1.19 (m, 7H) carboxamide 18 (3S)-1-(pyridin- ¹H NMR (300 MHz, DMSO-d₆) δ ppm 9.96 (s, (ESI(+)) 3-yl)-N-(4-{[1- 1H), 7.95 (d, J = 2.9 Hz, 1H), 7.85 (dd, J = 4.6, m/e 477 (3,3,3- 1.3 Hz, 1H), 7.55-7.48 (m, 2H), 7.16 (dd, (M + H)⁺ trifluoropropanoyl) J = 8.4, 4.5 Hz, 1H), 6.98-6.88 (m, 3H), 4.55 (dq, piperidin-4- J = 7.7, 3.8 Hz, 1H), 3.83 (ddd, J = 13.2, 6.8, 3.9 yl]oxy}phenyl) Hz, 1H), 3.74-3.49 (m, 5H), 3.48-3.38 (m, pyrrolidine-3- 2H), 2.38-2.06 (m, 3H), 2.02-1.80 (m, 2H), carboxamide 1.71-1.36 (m, 3H) 19 (3S)-N-[4-({1- ¹H NMR (300 MHz, DMSO-d₆) δ ppm 9.96 (s, (ESI(+)) [(2S)-2- 1H), 7.95 (d, J = 2.9 Hz, 1H), 7.85 (d, J = 4.6 m/e 451 methylbutanoyl] Hz, 1H), 7.55-7.48 (m, 2H), 7.16 (dd, J = 8.4, (M + H)⁺ piperidin-4- 4.5 Hz, 1H), 6.98-6.88 (m, 3H), 4.60-4.48 (m, yl}oxy)phenyl]- 1H), 4.03-3.69 (m, 2H), 3.54 (d, J = 8.6 Hz, 1-(pyridin-3- 1H), 3.47-3.37 (m, 2H), 3.33 (d, J = 4.6 Hz, yl)pyrrolidine-3- 1H), 3.27-3.17 (m, 1H), 2.72 (h, J = 6.7 Hz, carboxamide 1H), 2.35-2.01 (m, 2H), 2.02-1.79 (m, 2H), 1.65-1.10 (m, 5H), 0.98 (d, J = 6.7 Hz, 3H), 0.81 (t, J = 7.4 Hz, 3H)

Example 21 N-[1-(pyridin-3-yl)azetidin-3-yl]-4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}benzamide Example 21A tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidin-3-ylcarbamoyl)phenoxy)piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting benzyl 3-aminoazetidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 4-(1-(tert-butoxycarbonyl)piperidin-4-yloxy)benzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 21B benzyl 3-(4-(piperidin-4-yloxy)benzamido)azetidine-1-carboxylate

The title compound was prepared as described in Example 1D, substituting tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidin-3-ylcarbamoyl)phenoxy)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 21C benzyl 3-(4-(1-(2-(tetrahydro-2H-pyran-4-yl)acetyl)piperidin-4-yloxy)benzamido)azetidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting benzyl 3-(4-(piperidin-4-yloxy)benzamido)azetidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2-(tetrahydro-2H-pyran-4-yl)acetic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 21D N-(azetidin-3-yl)-4-(1-(2-(tetrahydro-2H-pyran-4-yl)acetyl)piperidin-4-yloxy)benzamide

The title compound was prepared as described in Example 1B, substituting benzyl 3-(4-(1-(2-(tetrahydro-2H-pyran-4-yl)acetyl)piperidin-4-yloxy)benzamido)azetidine-1-carboxylate for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 21E N-[1-(pyridin-3-yl)azetidin-3-yl]-4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}benzamide

The title compound was prepared as described in Example 1C, substituting N-(azetidin-3-yl)-4-(1-(2-(tetrahydro-2H-pyran-4-yl)acetyl)piperidin-4-yloxy)benzamide for tert-butyl 4-(4-(azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 8.83 (d, J=6.8 Hz, 1H), 7.93 (d, J=4.0 Hz, 1H), 7.85 (d, J=8.4 Hz, 3H), 7.27 (s, 2H), 7.26-7.11 (m, 1H), 7.05 (d, J=8.6 Hz, 2H), 6.87 (d, J=8.1 Hz, 1H), 4.86 (d, J=6.9 Hz, 1H), 4.71 (s, 1H), 4.28-4.19 (m, 2H), 3.93-3.64 (m, 6H), 2.30-2.23 (m, 2H), 2.05-1.67 (m, 3H), 1.52 (t, J=29.3 Hz, 5H), 1.32-0.81 (m, 3H); MS (ESI(+)) m/e 479 (M+H)⁺.

Example 23 4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)-N-[1-(pyridin-3-yl)azetidin-3-yl]benzamide

The title compound was prepared as described in Example 21, substituting (S)-2-methylbutanoic acid for 2-(tetrahydro-2H-pyran-4-yl)acetic acid in Example 21C. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 8.84 (d, J=7.0 Hz, 1H), 7.99-7.84 (m, 3H), 7.83 (s, 1H), 7.18 (dd, J=8.2, 4.6 Hz, 1H), 7.09-7.01 (m, 2H), 6.87 (ddd, J=8.2, 2.8, 1.4 Hz, 1H), 4.94-4.64 (m, 2H), 4.24 (t, J=7.5 Hz, 2H), 3.98-3.72 (m, 4H), 2.73 (h, J=6.7 Hz, 1H), 2.04-1.83 (m, 2H), 1.67-1.20 (m, 4H), 1.06-0.87 (m, 4H), 0.87-0.77 (m, 4H); MS (ESI(+)) m/e 437 (M+H)⁺.

Example 24 4-{[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]oxy}-N-[1-(pyridin-3-yl)azetidin-3-yl]benzamide

The title compound was prepared as described in Example 21, substituting 2-hydroxy-2-methylpropanoic acid for 2-(tetrahydro-2H-pyran-4-yl)acetic acid in Example 21C. ¹H NMR (500 MHz, DMSO-d₆) δ ppm 8.84 (d, J=7.0 Hz, 1H), 7.93 (dd, J=4.6, 1.3 Hz, 1H), 7.87-7.86 (m, 1H), 7.86 (s, 1H), 7.84 (s, 1H), 7.18 (dd, J=8.2, 4.6 Hz, 1H), 7.08-7.02 (m, 2H), 6.87 (ddd, J=8.2, 2.8, 1.4 Hz, 1H), 5.40 (s, 1H), 4.92-4.81 (m, 1H), 4.76-4.67 (m, 1H), 4.24 (t, J=7.5 Hz, 3H), 3.82 (dd, J=7.6, 5.9 Hz, 3H), 1.98-1.94 (m, 3H), 1.72-1.41 (m, 3H), 1.32 (s, 6H); MS (ESI(+)) m/e 439 (M+H)⁺.

Example 27 tert-butyl 4-(4-{[(3S)-1-(pyridin-3-yl)pyrrolidin-3-yl]carbamoyl}phenoxy)piperidine-1-carboxylate

The title compound was prepared as described in Example 21A, D and E, substituting (S)-benzyl 3-aminopyrrolidine-1-carboxylate for benzyl 3-aminoazetidine-1-carboxylate in Example 21A. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 8.43 (d, J=6.8 Hz, 1H), 7.94 (d, J=2.9 Hz, 1H), 7.87-7.80 (m, 3H), 7.15 (dd, J=8.4, 4.5 Hz, 1H), 7.03 (s, 1H), 7.00 (s, 1H), 6.90 (ddd, J=8.4, 3.0, 1.3 Hz, 1H), 4.71-4.55 (m, 2H), 3.73-3.53 (m, 3H), 3.44 (t, J=7.5 Hz, 1H), 3.18 (d, J=13.4 Hz, 2H), 3.17 (d, J=12.2 Hz, 2H), 2.34-2.19 (m, 1H), 2.14-1.97 (m, 1H), 1.98-1.82 (m, 2H), 1.63-1.43 (m, 2H), 1.40 (s, 9H); MS (ESI(+)) m/e 467 (M+H)⁺.

Example 28 tert-butyl 4-(4-{[(3R)-1-(pyridin-3-yl)pyrrolidin-3-yl]carbamoyl}phenoxy)piperidine-1-carboxylate

The title compound was prepared as described in Example 21A, D and E, substituting (R)-benzyl 3-aminopyrrolidine-1-carboxylate for benzyl 3-aminoazetidine-1-carboxylate in Example 21A. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 8.44 (d, J=6.8 Hz, 1H), 7.94 (d, J=2.9 Hz, 1H), 7.88-7.79 (m, 3H), 7.15 (dd, J=8.3, 4.5 Hz, 1H), 7.06-6.98 (m, 2H), 6.90 (ddd, J=8.4, 3.0, 1.4 Hz, 1H), 4.72-4.54 (m, 2H), 3.74-3.50 (m, 3H), 3.51-3.39 (m, 1H), 3.18 (d, J=13.6 Hz, 2H), 3.16 (d, J=11.9 Hz, 1H), 2.33-2.18 (m, 1H), 2.07 (dq, J=12.9, 6.5 Hz, 1H), 2.00-1.82 (m, 2H), 1.67-1.43 (m, 2H), 1.40 (s, 9H); MS (ESI(+)) m/e 467 (M+H)⁺.

Example 74 N-(4-{[1-(cyclopropylmethyl)piperidin-4-yl]oxy}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide

In a 20 mL vial was added N-(4-(piperidin-4-yloxy)phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide bis(2,2,2-trifluoroacetate) (67 mg, 0.12 mmol) dissolved in methanol (2.0 mL) followed by the addition of cyclopropanecarbaldehyde (10 mg, 0.14 mmol) dissolved in methanol (0.45 mL), followed by the addition of neat acetic acid (66 μL, 1.2 mmol). The mixture was shaken for 1 hour at 70° C. After that, 265 mg of MP-cyanoborohydride resin (2-3 mmol/g) was added and the resulting mixture was shaken at 70° C. overnight. The reaction mixture was filtered, checked by LC/MS and concentrated to dryness. The residues were dissolved in 1:1 DMSO/CH₃OH and purified by reverse phase HPLC. ¹H NMR (500 MHz, pyridine-d₅/D₂O) δ ppm 8.20-8.25 (m, 1H) 8.13 (d, J=2.75 Hz, 1H) 7.98-8.03 (m, 2H) 7.11 (dd, J=8.24, 4.58 Hz, 1H) 7.02-7.07 (m, 2H) 6.72-6.78 (m, 1H) 4.58 (d, J=2.75 Hz, 1H) 4.34 (t, J=6.71 Hz, 2H) 4.05 (t, J=7.63 Hz, 2H) 3.80-3.92 (m, 1H) 3.34 (s, 4H) 2.92 (d, J=7.32 Hz, 2H) 2.32-2.44 (m, 2H) 2.12 (s, 2H) 1.09-1.22 (m, 1H) 0.51-0.58 (m, 2H) 0.28-0.34 (m, 2H); MS (ESI(+)) m/e 407 (M+H).

The following Examples were prepared essentially as described in Example 74, substituting the appropriate aldehyde for cyclopropanecarbaldehyde. Some products were purified by flash chromatography while others were purified by reverse-phase HPLC. Accordingly, some Examples were isolated as trifluoroacetic acid salts.

TABLE 4 Ex Name ¹H NMR MS 75 N-(4-{[1-(2- ¹H NMR (500 MHz, pyridine-d₅/D₂O Temp = (ESI(+)) methylpentyl) 27° C.) δ ppm 8.23 (dd, J = 4.58, 1.22 Hz, 1 H) 8.13 m/e 437 piperidin-4- (d, J = 2.75 Hz, 1 H) 7.97-8.03 (m, 2 H) 7.06- (M + H)⁺ yl]oxy}phenyl)- 7.13 (m, 3 H) 6.71-6.77 (m, 1 H) 4.44 (s, 1 H) 1-(pyridin-3- 4.34 (t, J = 6.56 Hz, 2 H) 4.00-4.08 (m, 2 H) 3.78- yl)azetidine-3- 3.88 (m, 1 H) 2.96 (s, 2 H) 2.67 (s, 1 H) 2.34-2.48 carboxamide (m, J = 2.44 Hz, 3 H) 2.21 (s, 2 H) 1.97 (s, 2 H) 1.72-1.83 (m, 1 H) 1.15-1.45 (m, 3 H) 1.00- 1.10 (m, 1 H) 0.96 (d, J = 6.71 Hz, 3 H) 0.85 (t, J = 7.17 Hz, 3 H) 76 N-(4-{[1-(2- ¹H NMR (500 MHz, pyridine-d₅/D₂O Temp = (ESI(+)) methylpropyl) 27° C.) δ ppm 8.23 (dd, J = 4.73, 1.37 Hz, 1 H) 8.13 m/e 409 piperidin-4- (d, J = 2.75 Hz, 1 H) 7.97-8.04 (m, 2 H) 7.04- (M + H)⁺ yl]oxy}phenyl)- 7.15 (m, 3 H) 6.72-6.76 (m, 1 H) 4.40-4.47 (m, 1-(pyridin-3- 1 H) 4.34 (t, J = 6.56 Hz, 2 H) 3.99-4.09 (m, 2 H) yl)azetidine-3- 3.79-3.89 (m, 1 H) 2.91-3.00 (m, 2 H) 2.61- carboxamide 2.82 (m, 2 H) 2.36-2.45 (m, 2 H) 2.13-2.26 (m, J = 9.46 Hz, 2 H) 1.79-2.04 (m, 3 H) 0.92 (d, J = 6.41 Hz, 6 H) 77 N-(4-{[1-(3- ¹H NMR (500 MHz, pyridine-d₅/D₂O Temp = (ESI(+)) methylbutyl) 27° C.) δ ppm 8.21-8.26 (m, 1 H) 8.14 (d, J = 3.05 m/e 423 piperidin-4- Hz, 1 H) 7.98-8.03 (m, 2 H) 7.05-7.13 (m, 3 H) (M + H)⁺ yl]oxy}phenyl)- 6.71-6.77 (m, 1 H) 4.47-4.54 (m, 1 H) 4.34 (t, 1-(pyridin-3- J = 6.56 Hz, 2 H) 4.00-4.07 (m, 2 H) 3.80-3.89 yl)azetidine-3- (m, 1 H) 3.11 (s, 2 H) 2.87-3.06 (m, 2 H) 2.77- carboxamide 2.86 (m, 2 H) 2.22-2.33 (m, 2 H) 2.04 (s, 2 H) 1.47-1.61 (m, 3 H) 0.82 (d, J = 6.41 Hz, 6 H) 78 N-(4-{[1-(2- ¹H NMR (500 MHz, pyridine-d₅/D₂O Temp = (ESI(+)) ethylbutyl) 27° C.) δ ppm 8.23 (dd, J = 4.58, 1.22 Hz, 1 H) 8.13 m/e 437 piperidin-4- (d, J = 2.75 Hz, 1 H) 7.98-8.03 (m, 2 H) 7.06- (M + H)⁺ yl]oxy}phenyl)- 7.13 (m, 3 H) 6.71-6.76 (m, 1 H) 4.40-4.49 (m, 1-(pyridin-3- 1 H) 4.34 (t, J = 6.56 Hz, 2 H) 4.00-4.06 (m, 2 H) yl)azetidine-3- 3.78-3.88 (m, 1 H) 2.91-3.03 (m, 2 H) 2.57- carboxamide 2.77 (m, 2 H) 2.40-2.49 (m, J = 4.27, 2.14 Hz, 2 H) 2.14-2.28 (m, 2 H) 1.90-2.01 (m, J = 14.04 Hz, 2 H) 1.58 (s, 1 H) 1.29-1.45 (m, 4 H) 0.84 (t, J = 7.48 Hz, 6 H) 79 N-(4-{[1-(2,2- ¹H NMR (500 MHz, pyridine-d₅/D₂O Temp = (ESI(+)) dimethylpropyl) 27° C.) δ ppm 8.23 (dd, J = 4.58, 1.22 Hz, 1 H) 8.14 m/e 423 piperidin-4- (d, J = 2.75 Hz, 1 H) 7.99-8.01 (m, 2 H) 7.07- (M + H)⁺ yl]oxy}phenyl)- 7.13 (m, 3 H) 6.74 (d, J = 5.49 Hz, 1 H) 4.33 (t, 1-(pyridin-3- J = 6.56 Hz, 2 H) 4.00-4.06 (m, 2 H) 3.80-3.86 yl)azetidine-3- (m, 1 H) 2.73-2.81 (m, 2 H) 2.34-2.43 (m, 2 H) carboxamide 1.93-2.03 (m, 4 H) 1.76-1.88 (m, 2 H) 1.24- 1.34 (m, 1 H) 0.87 (s, 9 H) 80 N-(4-{[1-(2- ¹H NMR (500 MHz, pyridine-d₅/D₂O Temp = (ESI(+)) methylbutyl) 27° C.) δ ppm 8.21-8.24 (m, 1 H) 8.13 (d, J = 2.75 m/e 423 piperidin-4- Hz, 1 H) 8.00 (d, J = 9.16 Hz, 2 H) 7.07-7.14 (m, 3 (M + H)⁺ yl]oxy}phenyl)- H) 6.70-6.77 (m, 1 H) 4.29-4.39 (m, 3 H) 3.97- 1-(pyridin-3- 4.06 (m, 2 H) 3.77-3.86 (m, 1 H) 2.75-2.88 (m, yl)azetidine-3- 2 H) 2.45-2.56 (m, 4 H) 2.04-2.25 (m, 3 H) carboxamide 1.85 −1.97 (m, 2 H) 1.38-1.64 (m, 2 H) 0.81-0.93 (m, 6 H) 81 N-{4-[(1-propyl- (ESI(+)) piperidin-4- m/e 395 yl)oxy]phenyl}- (M + H)⁺ 1-(pyridin-3- yl)azetidine-3- carboxamide 82 N-(4-{[1-(2- ¹H NMR (500 MHz, pyridine-d₅/D₂O Temp = (ESI(+)) cyclopropyleth 27° C.) δ ppm 8.23 (dd, J = 4.58, 1.53 Hz, 1 H) 8.14 m/e 421 yl)piperidin-4- (d, J = 2.44 Hz, 1 H) 7.95-8.04 (m, 2 H) 7.05- (M + H)⁺ yl]oxy}phenyl)- 7.14 (m, 3 H) 6.69-6.78 (m, 1 H) 4.42-4.51 (m, 1-(pyridin-3- 1 H) 4.34 (t, J = 6.56 Hz, 2 H) 3.95-4.11 (m, 2 H) yl)azetidine-3- 3.79-3.89 (m, J = 8.24, 8.24 Hz, 1 H) 3.00-3.13 carboxamide (m, 2 H) 2.73-2.93 (m, 3 H) 2.40-2.48 (m, 1 H) 2.15-2.30 (m, 2 H) 2.01 (s, 2 H) 1.50-1.61 (m, J = 8.54 Hz, 2 H) 0.54-0.70 (m, 1 H) 0.33-0.42 (m, 2 H) 0.06 (t, J = 4.73 Hz, 2 H) 83 1-(pyridin-3- ¹H NMR (500 MHz, pyridine-d₅/D₂O Temp = (ESI(+)) yl)-N-(4-{[1- 27° C.) δ ppm 8.23 (dd, J = 4.58, 1.22 Hz, 1 H) 8.13 m/e 437 (tetrahydro- (d, J = 2.75 Hz, 1 H) 7.98-8.04 (m, 2 H) 7.03- (M + H)⁺ furan-3- 7.15 (m, 3 H) 6.70-6.77 (m, 1 H) 4.44-4.53 (m, ylmethyl) 1 H) 4.34 (t, J = 6.56 Hz, 2 H) 3.96-4.09 (m, 3 H) piperidin-4- 3.77-3.92 (m, 2 H) 3.55-3.74 (m, 2 H) 3.03- yl]oxylphenyl) 3.19 (m, 2 H) 2.86-3.04 (m, 2 H) 2.75-2.88 (m, azetidine-3- 2 H) 2.57-2.72 (m, 1 H) 2.19-2.34 (m, 2 H) 1.94- carboxamide 2.08 (m, 3 H) 1.56-1.71 (m, 1 H) 84 N-(4-{[1-(2,2- ¹H NMR (500 MHz, pyridine-d₅/D₂O Temp = (ESI(+)) dimethylbutyl) 27° C.) δ ppm 8.23 (dd, J = 4.73, 1.37 Hz, 1 H) 8.14 m/e 437 piperidin-4- (d, J = 2.44 Hz, 1 H) 7.97-8.02 (m, 2 H) 7.07- (M + H)⁺ yl]oxy}phenyl)- 7.13 (m, 3 H) 6.71-6.76 (m, 1 H) 4.28-4.38 (m, 1-(pyridin-3- 2 H) 4.00-4.06 (m, 2 H) 3.82 (s, 1 H) 2.72-2.82 yl)azetidine-3- (m, 2 H) 2.29-2.43 (m, 2 H) 1.91-2.07 (m, 4 H) carboxamide 1.75-1.88 (m, 2 H) 1.19-1.29 (m, J = 7.22, 7.22, 7.22 Hz, 3 H) 0.72-0.86 (m, 9 H)

Example 85 N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 10, substituting 4-bromopyridazine for 3-bromopyridine in Example 10C and 2-hydroxy-2-methylpropanoic acid for (S)-tetrahydrofuran-2-carboxylic acid in Example 10E. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.04 (s, 1H), 8.60 (d, J=6.0 Hz, 1H), 8.51 (d, J=3.0 Hz, 1H), 7.57-7.50 (m, 2H), 7.22-7.14 (m, 2H), 6.54 (dd, J=6.0, 3.0 Hz, 1H), 5.36 (s, 1H), 4.73 (bs, 2H), 4.30-3.96 (m, 4H), 3.87-3.60 (m, 1H), 2.71 (d, J=11.9 Hz, 1H), 1.82-1.72 (m, 2H), 1.67-1.42 (m, 2H), 1.35-1.31 (m, 8H); MS (ESI(+)) m/e 424 (M+H)⁺.

The following Examples were essentially prepared as described in Example 10, substituting 4-bromopyridazine for 3-bromopyridine in Example 10C and the appropriate acid for (S)-tetrahydrofuran-2-carboxylic acid in Example 10E. Some products were purified by flash chromatography while others were purified by reverse-phase HPLC. Accordingly, some Examples were isolated as trifluoroacetic acid salts.

TABLE 5 Ex Name MS 140 N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin- (ESI(+)) 4-yl)azetidine-3-carboxamide m/e 436 (M + H)⁺ 143 N-(4-{1-[(2S)-2-methylbutanoyl]piperidin-4-yl}phenyl)-1- (ESI(+)) (pyridazin-4-yl)azetidine-3-carboxamide m/e 422 (M + H)⁺ 144 N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-4- (ESI(+)) yl)azetidine-3-carboxamide m/e 448 (M + H)⁺ 145 1-(pyridazin-4-yl)-N-{4-[1-(tetrahydro-2H-pyran-4- (ESI(+)) ylacetyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide m/e 464 (M + H)⁺ 146 1-(pyridazin-4-yl)-N-{4-[1-(tetrahydro-2H-pyran-4- (ESI(+)) ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide m/e 564 (M + H)⁺ 525 N-{4-[1-(2-chlorobenzoyl)piperidin-4-yl]phenyl}1-1-(pyridazin-4- (ESI(+)) yl)azetidine-3-carboxamide m/e 476 (M + H)⁺ 526 1-(pyridazin-4-yl)-N-{4-[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4- (ESI(+)) yl]phenyl}azetidine-3-carboxamide m/e 449 (M + H)⁺ 527 N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-4- (ESI(+)) yl)azetidine-3-carboxamide m/e 420 (M + H)⁺ 528 N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4- (ESI(+)) yl)azetidine-3-carboxamide m/e 408 (M + H)⁺ 529 N-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4- (ESI(+)) yl)azetidine-3-carboxamide m/e 460 (M + H)⁺ 530 1-(pyridazin-4-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)piperidin-4- (ESI(+)) yl]phenyl}azetidine-3-carboxamide m/e 448 (M + H)⁺ 531 N-(4-{1-[(4-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1- (ESI(+)) (pyridazin-4-yl)azetidine-3-carboxamide m/e 474 (M + H)⁺ 532 N-(4-{1-[(3,5-difluorophenyl)acetyl]piperidin-4-yl}phenyl)-1- (ESI(+)) (pyridazin-4-yl)azetidine-3-carboxamide m/e 492 (M + H)⁺ 533 N-{4-[1-(3,4-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin- (ESI(+)) 4-yl)azetidine-3-carboxamide m/e 478 (M + H)⁺ 534 N-(4-{1-[(3-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1- (ESI(+)) (pyridazin-4-yl)azetidine-3-carboxamide m/e 474 (M + H)⁺ 535 1-(pyridazin-4-yl)-N-(4-{1-[3-(trifluoromethyl)benzoyl]piperidin-4- (ESI(+)) yl}phenyl)azetidine-3-carboxamide m/e 510 (M + H)⁺ 536 N-(4-{1-[(2,4-difluorophenyl)acetyl]piperidin-4-yl}phenyl)-1- (ESI(+)) (pyridazin-4-yl)azetidine-3-carboxamide m/e 492 (M + H)⁺ 537 1-(pyridazin-4-yl)-N-{4-[1-(1,3-thiazol-4-ylcarbonyl)piperidin-4- (ESI(+)) yl]phenyl}azetidine-3-carboxamide m/e 449 (M + H)⁺ 538 1-(pyridazin-4-yl)-N-{4-[1-(tetrahydrofuran-2-ylcarbonyl)piperidin- (ESI(+)) 4-yl]phenyl}azetidine-3-carboxamide m/e 436 (M + H)⁺ 539 N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)- (ESI(+)) 1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 462 (M + H)⁺ 540 N-(4-{1-[(2-fluorophenyl)acetyl]piperidin-4-yl}phenyl)-1- (ESI(+)) (pyridazin-4-yl)azetidine-3-carboxamide m/e 474 (M + H)⁺ 541 N-{4-[1-(cyclopropylcarbonyl)piperidin-4-yl]phenyl}-1-(pyridazin- (ESI(+)) 4-yl)azetidine-3-carboxamide m/e 406 (M + H)⁺ 542 1-(pyridazin-4-yl)-N-{4-[1-(tetrahydrofuran-3-ylcarbonyl)piperidin- (ESI(+)) 4-yl]phenyl}azetidine-3-carboxamide m/e 436 (M + H)⁺ 543 1-(pyridazin-4-yl)-N-{4-[1-(pyridin-2-ylcarbonyl)piperidin-4- (ESI(+)) yl]phenyl}azetidine-3-carboxamide m/e 443 (M + H)⁺ 544 N-{4-[1-(3-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4- (ESI(+)) yl)azetidine-3-carboxamide m/e 476 (M + H)⁺ 545 N-{4-[1-(4-chlorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4- (ESI(+)) yl)azetidine-3-carboxamide m/e 476 (M + H)⁺ 546 N-{4-[1-(2-methyl-2-phenylpropanoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-4-yl)azetidine-3-carboxamide m/e 484 (M + H)⁺ 547 N-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin- (ESI(+)) 4-yl)azetidine-3-carboxamide m/e 478 (M + H)⁺ 548 N-{441-(methoxyacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-4- (E SI(+)) yl)azetidine-3-carboxamide m/e 410 (M + H)⁺ 549 1-(pyridazin-4-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)piperidin-4- (ESI(+)) yl]phenyl}azetidine-3-carboxamide m/e 448 (M + H)⁺ 550 1-(pyridazin-4-yl)-N-[4-(1-{[3- (ESI(+)) (trifluoromethyl)phenyl]acetyl}piperidin-4-yl)phenyl]azetidine-3- m/e 524 carboxamide (M + H)⁺ 551 N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4- (ESI(+)) yl)azetidine-3-carboxamide m/e 460 (M + H)⁺ 552 N-{4-[1-(3,5-difluorob enzoyl)piperidin-4-yl]phenyl}-1-(pyridazin- (ESI(+)) 4-yl)azetidine-3-carboxamide m/e 478 (M + H)⁺ 553 1-(pyridazin-4-yl)-N-(4-{1-[4-(trifluoromethyl)benzoyl]piperidin-4- (ESI(+)) yl}phenyl)azetidine-3-carboxamide m/e 510 (M + H)⁺ 554 N-{4-[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}1-1-(pyridazin-4- (ESI(+)) yl)azetidine-3-carboxamide m/e 460 (M + H)⁺ 555 1-(pyridazin-4-yl)-N-(4-{1-[4-(trifluoromethoxy)benzoyl]piperidin- (ESI(+)) 4-yl}phenyl)azetidine-3-carboxamide m/e 526 (M + H)⁺ 556 N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4- (ESI(+)) yl)azetidine-3-carboxamide m/e 422 (M + H)⁺ 557 1-(pyridazin-4-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4- (ESI(+)) yl]phenyl}azetidine-3-carboxamide m/e 448 (M + H)⁺ 558 N-(4-{1-[difluoro(phenyl)acetyl]piperidin-4-yl}phenyl)-1- (ESI(+)) (pyridazin-4-yl)azetidine-3-carboxamide m/e 492 (M + H)⁺ 559 N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-4-yl)azetidine-3-carboxamide m/e 422 (M + H)⁺ 560 N-(4-{1-[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl}phenyl)- (ESI(+)) 1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 484 (M + H)⁺ 561 1-(pyridazin-4-yl)-N-[4-(1-{[4- (ESI(+)) (trifluoromethoxy)phenyl]acetyllpiperidin-4-yl)phenyl]azetidine-3- m/e 540 carboxamide (M + H)⁺ 562 1-(pyridazin-4-yl)-N-(4-{1-[3-(trifluoromethoxy)benzoyl]piperidin- (ESI(+)) 4-yl}phenyl)azetidine-3-carboxamide m/e 526 (M + H)⁺ 563 1-(pyridazin-4-yl)-N-[4-(1-{[4- (ESI(+)) (trifluoromethyl)phenyl]acetyl}piperidin-4-yl)phenyl]azetidine-3- m/e 524 carboxamide (M + H)⁺

Example 86 N-{4-[1-(cyclohexylmethyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 74, substituting N-(4-(piperidin-4-yl)phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide for N-(4-(piperidin-4-yloxy)phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide and cyclohexanecarbaldehyde for cyclopropanecarbaldehyde. ¹H NMR (500 MHz, pyridine-d₅/D₂O) δ ppm 8.23 (dd, J=4.58, 1.22 Hz, 1H) 8.13 (d, J=2.75 Hz, 1H) 7.99 (d, J=8.54 Hz, 2H) 7.31-7.36 (m, 2H) 7.11 (dd, J=8.24, 4.27 Hz, 1H) 6.71-6.75 (m, 1H) 4.32 (t, J=6.56 Hz, 2H) 3.98-4.05 (m, 2H) 3.79-3.89 (m, 1H) 3.62-3.71 (m, 2H) 2.69-2.95 (m, 5H) 2.37-2.49 (m, 2H) 1.75-2.00 (m, 5H) 1.46-1.65 (m, 3H) 0.90-1.24 (m, 5H); (ESI(+)) m/e 433 (M+H).

The following Examples were prepared essentially as described in Example 74, substituting N-(4-(piperidin-4-yl)phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide for N-(4-(piperidin-4-yloxy) phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide and the appropriate aldehyde for cyclopropanecarbaldehyde. Some products were purified by flash chromatography while others were purified by reverse-phase HPLC. Accordingly, some Examples were isolated as trifluoroacetic acid salts.

TABLE 6 Ex Name ¹H NMR MS 87 N-{4-[1-(3,3- ¹H NMR (500 MHz, pyridine-d₅/D₂O) δ ppm 8.23 (ESI(+)) dimethylbutyl) (dd, J = 4.73, 1.37 Hz, 1 H) 8.13 (d, J = 2.75 Hz, 1 H) m/e 421 piperidin-4- 7.98 (d, J = 8.54 Hz, 2 H) 7.29-7.32 (m, 2 H) 7.11 (M + H)⁺ yl]phenyl}-1- (dd, J = 7.93, 4.88 Hz, 1 H) 6.69-6.75 (m, 1 H) 4.32 (pyridin-3- (t, J = 6.71 Hz, 2 H) 3.98-4.04 (m, 2 H) 3.79-3.87 yl)azetidine- (m, 1 H) 3.68 (s, 2 H) 3.08-3.15 (m, 2 H) 2.80- 3- 2.92 (m, 2 H) 2.71-2.79 (m, 1 H) 2.34-2.46 (m, 2 carboxamide H) 1.90-1.99 (m, 2 H) 1.71-1.78 (m, 2 H) 0.87 (s, 9 H) 88 N-{4-[1- ¹H NMR (500 MHz, pyridine-d₅/D₂O) δ ppm 8.23 (ESI(+)) (cyclopentyl- (dd, J = 4.88, 1.22 Hz, 1 H) 8.13 (d, J = 2.75 Hz, 1 H) m/e 419 methyl) 7.99 (d, J = 8.54 Hz, 2 H) 7.31-7.35 (m, 2 H) 7.11 (M + H)⁺ piperidin-4- (dd, J = 8.09, 4.73 Hz, 1 H) 6.70-6.75 (m, 1 H) 4.33 yl]phenyl}-1- (t, J = 6.56 Hz, 2 H) 3.97-4.05 (m, 2 H) 3.77-3.85 (pyridin-3- (m, 1 H) 3.56-3.71 (m, 2 H) 2.98 (d, J = 6.71 Hz, 2 yl)azetidine- H) 2.69-2.86 (m, J = 12.21, 12.21 Hz, 3 H) 2.34- 3- 2.49 (m, 2 H) 2.19-2.31 (m, 1 H) 1.78-1.97 (m, 4 carboxamide H) 1.35-1.57 (m, 4 H) 1.17-1.28 (m, 2 H) 89 N-{4-[1-(2,2- ¹H NMR (500 MHz, pyridine-d₅/D₂O) δ ppm 8.23 (ESI(+)) dimethylbutyl) (dd, J = 4.58, 1.22 Hz, 1 H) 8.14 (d, J = 2.75 Hz, 1 H) m/e 421 piperidin-4- 8.02 (d, J = 8.54 Hz, 2 H) 7.32 (d, J = 8.24 Hz, 2 H) (M + H)⁺ yl]phenyl}-1- 7.11 (dd, J = 8.24, 4.58 Hz, 1 H) 6.71-6.75 (m, 1 H) (pyridin-3- 4.33 (t, J = 6.56 Hz, 2 H) 3.99-4.05 (m, 2 H) 3.79- yl)azetidine- 3.86 (m, 1 H) 2.89-2.97 (m, 2 H) 2.29-2.50 (m, 3- J = 59.51 Hz, 3 H) 2.14 (d, J = 3.97 Hz, 2 H) 1.84- carboxamide 1.97 (m, 2 H) 1.71-1.78 (m, 2 H) 1.30 (q, J = 7.63 Hz, 2 H) 0.88 (s, 6 H) 0.82 (t, J = 7.48 Hz, 3 H) 90 N-{4-[1-(2- ¹H NMR (500 MHz, pyridine-d₅/D₂O) δ ppm 8.23 (ESI(+)) methylpentyl) (dd, J = 4.73, 1.37 Hz, 1 H) 8.13 (d, J = 2.75 Hz, 1 H) m/e 421 piperidin-4- 7.99 (d, J = 8.54 Hz, 2 H) 7.30-7.37 (m, 2 H) 7.11 (M + H)⁺ yl]phenyl}-1- (dd, J = 8.24, 4.27 Hz, 1 H) 6.69-6.77 (m, 1 H) 4.28- (pyridin-3- 4.36 (m, 2 H) 3.96-4.06 (m, 2 H) 3.77-3.87 (m, 1 yl)azetidine- H) 3.53 (s, 2 H) 2.55-2.91 (m, 5 H) 2.23-2.42 (m, 3- 2 H) 1.81-1.95 (m, J = 6.71 Hz, 3 H) 1.04-1.47 (m, carboxamide 4 H) 1.03 (t, J = 6.41 Hz, 3 H) 0.85 (t, J = 7.17 Hz, 3 H) 91 N-[4-(1- ¹H NMR (500 MHz, pyridine-d₅/D₂O) δ ppm 8.20- (ESI(+)) butylpiperidin- 8.27 (m, 1 H) 8.13 (d, J = 3.05 Hz, 1 H) 7.99 (d, m/e 393 4- J = 8.54 Hz, 2 H) 7.30-7.35 (m, 2 H) 7.08-7.12 (m, (M + H)⁺ yl)phenyl]-1- 1 H) 6.68-6.74 (m, 1 H) 4.32 (t, J = 6.56 Hz, 2 H) (pyridin-3- 3.97-4.06 (m, 2 H) 3.78-3.86 (m, 1 H) 3.56-3.69 yl)azetidine- (m, 2 H) 2.92-3.03 (m, 2 H) 2.66-2.87 (m, 3 H) 3- 2.29-2.45 (m, 2 H) 1.91 (d, J = 13.73 Hz, 2 H) 1.65- carboxamide 1.77 (m, 2 H) 1.10-1.31 (m, 2 H) 0.79 (t, J = 7.32 Hz, 3 H) 92 N-{4-[1-(2- ¹H NMR (500 MHz, pyridine-d₅/D₂O) δ ppm 8.23 (ESI(+)) ethylbutyl) (d, J = 4.58 Hz, 1 H) 8.13 (d, J = 2.75 Hz, 1 H) 7.99 (d, m/e 421 piperidin-4- J = 8.54 Hz, 2 H) 7.33 (d, J = 8.54 Hz, 2 H) 7.09-7.11 (M + H)⁺ yl]phenyl}-1- (m, 1 H) 6.70-6.74 (m, 1 H) 4.32 (t, J = 6.56 Hz, 2 (pyridin-3- H) 3.97-4.05 (m, 2 H) 3.78-3.86 (m, 1 H) 3.43- yl)azetidine- 3.61 (m, 2 H) 2.55-2.95 (m, 5 H) 2.22-2.43 (m, 2 3- H) 1.90 (d, J = 13.12 Hz, 2H) 1.67-1.78 (m, 1 H) carboxamide 1.30-1.50 (m, 4 H) 0.85 (t, J = 7.48 Hz, 6 H) 93 N-{4-[1-(3- ¹H NMR (500 MHz, pyridine-d₅/D₂O) δ ppm 8.19- (ESI(+)) methylbutyl) 8.26 (m, 1 H) 8.13 (d, J = 2.75 Hz, 1 H) 7.99 (d, m/e 407 piperidin-4- J = 8.54 Hz, 2 H) 7.29-7.34 (m, 2 H) 7.11 (dd, (M + H)⁺ yl]phenyl}-1- J = 8.24, 4.58 Hz, 1 H) 6.67-6.76 (m, 1 H) 4.32 (t, (pyridin-3- J = 6.56 Hz, 2 H) 3.98-4.04 (m, 2 H) 3.77-3.87 (m, yl)azetidine- 1 H) 3.57-3.69 (m, 2 H) 2.95-3.05 (m, 2 H) 2.67- 3- 2.87 (m, 3 H) 2.29-2.44 (m, 2 H) 1.84-1.98 (m, 2 carboxamide H) 1.60-1.71 (m, 2 H) 1.39-1.58 (m, 1 H) 0.82 (d, J = 6.71 Hz, 6 H) 94 N-{4-[1-(2- ¹H NMR (500 MHz, pyridine-d₅/D₂O) δ ppm 8.21- (ESI(+)) methylpropyl) 8.27 (m, 1 H) 8.14 (d, J = 2.75 Hz, 1 H) 7.99 (d, m/e 393 piperidin-4- J = 8.54 Hz, 2 H) 7.32 (d, J = 8.54 Hz, 2 H) 7.11 (dd, (M + H)⁺ yl]phenyl}-1- J = 8.09, 4.73 Hz, 1 H) 6.70-6.75 (m, 1 H) 4.33 (t, (pyridin-3- J = 6.56 Hz, 2 H) 3.97-4.04 (m, 2 H) 3.78-3.87 (m, yl)azetidine- 1 H) 3.27-3.41 (m, 2 H) 2.62 (s, 1 H) 2.38-2.52 3- (m, 4 H) 2.10-2.26 (m, J = 22.28 Hz, 2 H) 1.90-1.99 carboxamide (m, 1 H) 1.81-1.88 (m, 2 H) 0.95 (d, J = 6.41 Hz, 6 H) 95 N-[4-(1- ¹H NMR (500 MHz, pyridine-d₅/D₂O) δ ppm 8.21- (ESI(+)) propylpiperidin- 8.25 (m, 1 H) 8.10-8.15 (m, 1 H) 7.98 (d, J = 8.54 m/e 379 4- Hz, 2 H) 7.31 (d, J = 8.54 Hz, 2 H) 7.11 (dd, J = 8.24, (M + H)⁺ yl)phenyl]-1- 4.58 Hz, 1 H) 6.71-6.76 (m, 1 H) 4.32 (t, J = 6.56 (pyridin-3- Hz, 2 H) 3.99-4.04 (m, 2 H) 3.77-3.89 (m, 1 H) yl)azetidine- 3.55-3.66 (m, 2 H) 2.86-2.98 (m, 2 H) 2.64-2.86 3- (m, 3 H) 2.30-2.46 (m, 2 H) 1.90 (d, J = 14.04 Hz, 2 carboxamide H) 1.70-1.81 (m, 2 H) 0.78 (t, J = 7.32 Hz, 3 H)

Example 141 (3S)—N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)pyrrolidine-3-carboxamide Example 141A (S)-tert-butyl 4-(4-(1-((benzyloxy)carbonyl)pyrrolidine-3-carboxamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting (S)-1-((benzyloxy)carbonyl)pyrrolidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid and tert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate.

Example 141B (S)-tert-butyl 4-(4-(pyrrolidine-3-carboxamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1B, substituting (S)-tert-butyl 4-(4-(1-((benzyloxy)carbonyl)pyrrolidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 141C (S)-tert-butyl 4-(4-(1-(pyridazin-4-yl)pyrrolidine-3-carboxamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1C, substituting (S)-tert-butyl 4-(4-(pyrrolidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate and 4-bromopyridazine for 3-bromopyridine.

Example 141D (S)—N-(4-(piperidin-4-yl)phenyl)-1-(pyridazin-4-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 141E (3S)—N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting (S)—N-(4-(piperidin-4-yl)phenyl)-1-(pyridazin-4-yl)pyrrolidine-3-carboxamide for tert-butyl 4-(4-aminophenoxy)piperidine-1-carboxylate and 2-hydroxy-2-methylpropanoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.07 (s, 1H), 8.68-8.61 (m, 1H), 8.61-8.50 (m, 1H), 7.52 (t, J=6.8 Hz, 2H), 7.17 (d, J=8.6 Hz, 2H), 6.62 (dd, J=6.3, 3.2 Hz, 1H), 5.35 (s, 1H), 3.73-3.34 (m, 8H), 2.73 (dd, J=13.9, 10.2 Hz, 2H), 2.40-2.06 (m, 2H), 1.76 (d, J=11.0 Hz, 2H), 1.64-1.38 (m, 2H), 1.33 (s, 6H); MS (ESI(+)) m/e 438 (M+H)⁺.

Example 142 (3S)—N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting (S)—N-(4-(piperidin-4-yl)phenyl)-1-(pyridazin-4-yl)pyrrolidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and cyclopentylacetic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.07 (s, 1H), 8.64 (dd, J=3.1, 0.9 Hz, 1H), 8.57 (dd, J=6.2, 0.9 Hz, 1H), 7.54 (s, 1H), 7.51 (s, 1H), 7.21-7.13 (m, 2H), 6.61 (dd, J=6.2, 3.1 Hz, 1H), 3.68-3.41 (m, 8H), 3.18-3.00 (m, 1H), 2.78-2.64 (m, 1H), 2.42-2.06 (m, 5H), 1.83-1.69 (m, 4H), 1.65-1.20 (m, 6H), 1.22-1.04 (m, 2H); MS (ESI(+)) m/e 462 (M+H)⁺.

Example 147 N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide Example 147A tert-butyl 4-(4-(1-(6-chloropyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate

In a 50 mL round-bottomed flask was added tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate (918 mg, 2.55 mmol) and diisopropylethylamine (0.558 ml, 3.19 mmol) in ethanol (10.6 ml). 3,6-dichloropyridazine (317 mg, 2.128 mmol) was added as a solid in a single portion. The reaction was stirred overnight at 45° C.; and the reaction was cooled and concentrated. Dichloromethane and water were added and the layers were separated. The aqueous layer was extracted three times with dichloromethane and the combined organics were dried with magnesium sulfate, filtered and concentrated by rotary evaporation. The residue was purified by regular phase flash column chromatography to give the title compound.

Example 147B tert-butyl 4-(4-(1-(pyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate

To a 50 mL round-bottomed flask was added tert-butyl 4-(4-(1-(6-chloropyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate (550 mg, 1.165 mmol) and Pd/C (93 mg, 0.087 mmol). The flask was flushed with nitrogen for 10 minutes and ethanol (11.7 ml) was added. Triethylamine (0.162 ml, 1.165 mmol) and cyclohexa-1,4-diene (654 mg, 8.16 mmol) were added and the reaction was stirred at 80° C. for 1 hour, cooled and filtered through diatomaceous earth. The filtrate was concentrated in vacuo and the residue was purified by regular phase flash column chromatography to give the title compound.

Example 147C N-(4-(piperidin-4-yl)phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting tert-butyl 4-(4-(1-(pyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 147D N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(4-(piperidin-4-yl)phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2-methylpropanoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.03 (s, 1H), 8.56 (dd, J=4.5, 1.3 Hz, 1H), 7.52 (dd, J=9.2, 4.7 Hz, 2H), 7.40 (ddd, J=13.5, 7.9, 2.8 Hz, 1H), 7.18 (d, J=8.6 Hz, 2H), 6.82 (dd, J=8.9, 1.3 Hz, 1H), 4.55 (d, J=12.0 Hz, 1H), 4.32-3.90 (m, 5H), 3.83-3.54 (m, 1H), 3.10 (t, J=12.9 Hz, 1H), 2.89 (kept, J=6.7 Hz, 1H), 2.71 (ddd, J=28.5, 16.0, 11.7 Hz, 1H), 1.77 (d, J=12.3 Hz, 2H), 1.60-1.10 (m, 4H), 1.01 (t, J=6.0 Hz, 6H); MS (ESI(+)) m/e 408 (M+H)⁺.

The following Examples were prepared essentially as described in Example 1A, substituting N-(4-(piperidin-4-yl)phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for tertbutyl 4-(4-aminophenoxy)piperidine-1-carboxylate and the appropriate carboxylic acid for 1-(benzyloxycarbonyl) azetidine-3-carboxylic acid. Some products were purified by flash chromatography while others were purified by reverse-phase HPLC. Accordingly, some Examples were isolated as trifluoroacetic acid salts.

TABLE 7 Ex Name MS 316 N-[4-(1-acetylpiperidin-4-yl)phenyl]-1-(pyridazin-3- (ESI(+)) yl)azetidine-3-carboxamide m/e 380 (M + H)⁺ 317 N-[4-(1-butanoylpiperidin-4-yl)phenyl]-1-(pyridazin- (ESI(+)) 3-yl)azetidine-3-carboxamide m/e 408 (M + H)⁺ 318 N-[4-(1-pentanoylpiperidin-4-yl)phenyl]-1-(pyridazin- (ESI(+)) 3-yl)azetidine-3-carboxamide m/e 422 (M + H)⁺ 319 N-{4-[1-(2-methylbutanoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 422 (M + H)⁺ 320 N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 422 (M + H)⁺ 321 N-[4-(1-hexanoylpiperidin-4-yl)phenyl]-1-(pyridazin- (ESI(+)) 3-yl)azetidine-3-carboxamide m/e 436 (M + H)⁺ 322 N-{4-[1-(2-methylpentanoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 436 (M + H)⁺ 323 N-{4-[1-(3-methylpentanoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 436 (M + H)⁺ 324 N-{4-[1-(4-methylpentanoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 436 (M + H)⁺ 325 N-{4-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 436 (M + H)⁺ 326 N-{4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 436 (M + H)⁺ 327 N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 436 (M + H)⁺ 328 N-{4-[1-(2-ethylbutanoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 436 (M + H)⁺ 329 N-[4-(1-heptanoylpiperidin-4-yl)phenyl]-1-(pyridazin- (ESI(+)) 3-yl)azetidine-3-carboxamide m/e 450 (M + H)⁺ 330 N-{4-[1-(but-3-enoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 406 (M + H)⁺ 331 N-{4-[1-(pent-4-enoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 420 (M + H)⁺ 332 1-(pyridazin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl) (ESI(+)) piperidin-4-yl]phenyl}azetidine-3-carboxamide m/e 448 (M + H)⁺ 333 N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 410 (M + H)⁺ 334 N-(4-{1-[(methylsulfanyl)acetyl]piperidin-4-yl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 426 (M + H)⁺ 335 N-(4-{1-[(2-methoxyethoxy)acetyl]piperidin-4-yl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 454 (M + H)⁺ 336 N-{4-[1-[3-nitropropanoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 439 (M + H)⁺ 337 N-(4-{1-[3-(methylsulfanyl)propanoyl]piperidin-4- (ESI(+)) yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 440 (M + H)⁺ 338 N-{4-[1-(pent-4-ynoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 418 (M + H)⁺ 339 N-{4-[1-(cyclohexylcarbonyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 448 (M + H)⁺ 340 N-{4-[1-(cyclohexylacetyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 462 (M + H)⁺ 341 N-{4-[1-(3-methylbenzoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 456 (M + H)⁺ 342 N-{4-[1-(2-hydroxybenzoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 458 (M + H)⁺ 343 N-{4-[1-(3-hydroxybenzoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 458 (M + H)⁺ 344 N-{4-[1-(4-hydroxybenzoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 458 (M + H)⁺ 345 N-{4-[1-(2-methoxybenzoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 472 (M + H)⁺ 346 N-{4-[1-(3-methoxybenzoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 472 (M + H)⁺ 347 N-{4-[1-(4-methoxybenzoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 472 (M + H)⁺ 348 N-{4-[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 460 (M + H)⁺ 349 N-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 460 (M + H)⁺ 350 N-{4-[1-(2-chlorobenzoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 476 (M + H)⁺ 351 N-{4-[1-(3-chlorobenzoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 476 (M + H)⁺ 352 N-{4-[1-(3-cyanobenzoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 467 (M + H)⁺ 353 N-{4-[1-(4-cyanobenzoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 467 (M + H)⁺ 354 1-(pyridazin-3-yl)-N-(4-{1-[3-(trifluoromethyl) (ESI(+)) benzoyl]piperidin-4-yl}phenyl)azetidine-3- m/e 510 carboxamide (M + H)⁺ 355 1-(pyridazin-3-yl)-N-(4-{1-[4-(trifluoromethyl) (ESI(+)) benzoyl]piperidin-4-yl}phenyl)azetidine-3- m/e 510 carboxamide (M + H)⁺ 356 1-(pyridazin-3-yl)-N-(4-{1-[3-(trifluoromethoxy) (ESI(+)) benzoyl]piperidin-4-yl}phenyl)azetidine-3- m/e 526 carboxamide (M + H)⁺ 357 N-{4-[1-(2,3-dimethylbenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 470 (M + H)⁺ 358 N-{4-[1-(2,4-dimethylbenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 470 (M + H)⁺ 359 N-{4-[1-(2,5-dimethylbenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 470 (M + H)⁺ 360 N-{4-[1-(3,4-dimethylbenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 470 (M + H)⁺ 361 N-{4-[1-(3,5-dimethylbenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 470 (M + H)⁺ 362 N-{4-[1-(2,4-dichlorobenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 510 (M + H)⁺ 363 N-{4-[1-(2,5-dichlorobenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 510 (M + H)⁺ 364 N-{4-[1-(3,4-dichlorobenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 510 (M + H)⁺ 365 N-{4-[1-(3,5-dichlorobenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 510 (M + H)⁺ 366 N-(4-{1-[(2-fluorophenyl)acetyl]piperidin-4-yl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 474 (M + H)⁺ 367 N-(4-{1-[(3-fluorophenyl)acetyl]piperidin-4-yl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 474 (M + H)⁺ 368 N-(4-{1-[(4-fluorophenyl)acetyl]piperidin-4-yl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 474 (M + H)⁺ 369 N-(4-{1-[(2-chlorophenyl)acetyl]piperidin-4-yl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 490 (M + H)⁺ 370 N-(4-{1-[(4-chlorophenyl)acetyl]piperidin-4-yl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 490 (M + H)⁺ 371 1-(pyridazin-3-yl)-N-[4-(1-{[4- (ESI(+)) (trifluoromethyl)phenyl]acetyl}piperidin-4-yl)phenyl] m/e 524 azetidine-3-carboxamide (M + H)⁺ 372 N-(4-{1-[(3,5-dimethylphenyl)acetyl]piperidin-4-yl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 484 (M + H)⁺ 373 N-(4-{1-[(2,5-difluorophenyl)acetyl]piperidin-4-yl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 492 (M + H)⁺ 374 N-(4-{1-[(3,4-dichlorophenyl)acetyl]piperidin-4-yl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 525 (M + H)⁺ 375 N-{4-[1-(furan-3-ylcarbonyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 432 (M + H)⁺ 376 1-(pyridazin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl) (ESI(+)) piperidin-4-yl]phenyl}azetidine-3-carboxamide m/e 448 (M + H)⁺ 377 N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]piperidin- (ESI(+)) 4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3- m/e 462 carboxamide (M + H)⁺ 378 N-(4-{1-[(5-methylpyrazin-2-yl)carbonyl]piperidin- (ESI(+)) 4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 458 (M + H)⁺ 379 N-(4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4- (ESI(+)) yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 420 (M + H)⁺ 380 N-{4-[1-(3-ethoxypropanoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 438 (M + H)⁺ 381 N-(4-{1-[(1-phenylcyclopropyl)carbonyl]piperidin-4- (ESI(+)) yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 482 (M + H)⁺ 382 1-(pyridazin-3-yl)-N-(4-{1-[(pyrimidin-2- (ESI(+)) ylsulfanyl)acetyl]piperidin-4-yl}phenyl)azetidine-3- m/e 490 carboxamide (M + H)⁺ 383 N-(4-{1-[(1-acetylpiperidin-4-yl)carbonyl]piperidin-4- (ESI(+)) yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 491 (M + H)⁺ 384 N-(4-{14(3,5-difluorophenyl)acetyl]piperidin-4-yl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 492 (M + H)⁺ 385 N-{4-[1-(N-acetyl-L-leucyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 493 (M + H)⁺ 386 N-{4-[1-(diphenylacetyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 532 (M + H)⁺ 387 N-{4-[1-(3-fluoro-2-methylbenzoyl)piperidin-4- (ESI(+)) yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 474 (M + H)⁺ 388 N-{4-[1-(5-fluoro-2-methylbenzoyl)piperidin-4- (ESI(+)) yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 474 (M + H)⁺ 389 N-{4-[1-(3-fluoro-4-methylbenzoyl)piperidin-4- (ESI(+)) yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 474 (M + H)⁺ 390 N-{4-[1-(2,3-difluorobenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 478 (M + H)⁺ 391 N-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 478 (M + H)⁺ 392 N-(4-{1-[4-(propan-2-yl)benzoyl]piperidin-4-yl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 484 (M + H)⁺ 393 N-{4-[1-(4-tert-butylbenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 498 (M + H)⁺ 394 N-(4-{1-[2-fluoro-5-(trifluoromethyl)benzoyl] (ESI(+)) piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine- m/e 528 3-carboxamide (M + H)⁺ 395 N-(4-{1-[2-chloro-5-(trifluoromethyl)benzoyl] (ESI(+)) piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine- m/e 544 3-carboxamide (M + H)⁺ 397 N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 448 (M + H)⁺ 398 N-(4-{1-[(4-methylphenoxy)acetyl]piperidin-4-yl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 486 (M + H)⁺ 399 N-(4-{1-[(2S)-2-phenylbutanoyl]piperidin-4-yl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 484 (M + H)⁺ 400 N-{4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 478 (M + H)⁺ 401 N-{4-[1-(4-chlorobenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 476 (M + H)⁺ 402 N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 422 (M + H)⁺ 403 1-(pyridazin-3-yl)-N-[4-(1-{[3- (ESI(+)) (trifluoromethyl)phenyl]acetyl}piperidin-4-yl)phenyl] m/e 524 azetidine-3-carboxamide (M + H)⁺ 404 N-(4-{1-[(3-chlorophenyl)acetyl]piperidin-4-yl}phenyl)- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 490 (M + H)⁺ 405 N-(4-{1-[(2,4-dichlorophenyl)acetyl]piperidin-4-yl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 524 (M + H)⁺ 406 N-{4-[1-(naphthalen-1-ylcarbonyl)piperidin-4-yl] (ESI(+)) phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 492 (M + H)⁺ 407 N-(4-{1-[(2R)-2-methoxy-2-phenylacetyl]piperidin- (ESI(+)) 4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3- m/e 486 carboxamide (M + H)⁺ 408 N-(4-{1-[N-(furan-2-ylcarbonyl)glycyl]piperidin-4- (ESI(+)) yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 489 (M + H)⁺ 409 N-(4-{1-[(benzyloxy)acetyl]piperidin-4-yl}phenyl)- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 486 (M + H)⁺ 410 N-{4-[1-(naphthalen-1-ylacetyl)piperidin-4-yl] (ESI(+)) phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 506 (M + H)⁺ 411 N-{4-[1-(cyclopropylcarbonyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 406 (M + H)⁺ 412 1-(pyridazin-3-yl)-N-{4-[1-(tetrahydrofuran-2- (ESI(+)) ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3- m/e 436 carboxamide (M + H)⁺ 413 N-{4-[1-(N-benzoylglycyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 499 (M + H)⁺ 414 1-(pyridazin-3-yl)-N-{4-[1-(tetrahydrofuran-3- (ESI(+)) ylcarbonyl)piperidin-4-yl]phenyl}azetidine-3- m/e 436 carboxamide (M + H)⁺ 415 1-(pyridazin-3-yl)-N-(4-{1-[4-(thiophen-2-yl) (ESI(+)) butanoyl]piperidin-4-yl}phenyl)azetidine-3- m/e 490 carboxamide (M + H)⁺ 416 N-{4-[1-(2,5-difluorobenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 478 (M + H)⁺ 417 N-{4-[1-(cyclobutylcarbonyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 420 (M + H)⁺ 418 N-[4-(1-{N-[(4-methylphenyl)sulfonyl]glycyl}piperidin- (ESI(+)) 4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 549 (M + H)⁺ 419 N-(4-{1-[(2,3-difluorophenyl)acetyl]piperidin-4-yl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 492 (M + H)⁺ 420 N-(4-{1-[(2S)-2-methoxy-2-phenylacetyl]piperidin-4- (ESI(+)) yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 486 (M + H)⁺ 421 N-{4-[1-(naphthalen-2-ylacetyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 506 (M + H)⁺ 422 N-{4-[1-(3-phenylpropanoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 470 (M + H)⁺ 423 N-(4-{1-[(2,6-dichlorophenyl)acetyl]piperidin-4- (ESI(+)) yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 524 (M + H)⁺ 424 N-(4-{1-[3-(phenylsulfonyl)propanoyl]piperidin-4- (ESI(+)) yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 534 (M + H)⁺ 425 1-(pyridazin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl) (ESI(+)) piperidin-4-yl]phenyl}azetidine-3-carboxamide m/e 448 (M + H)⁺ 426 N-(4-{1-[(2,5-dimethylfuran-3-yl)carbonyl]piperidin- (ESI(+)) 4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3- m/e 460 carboxamide (M + H)⁺ 427 N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 420 (M + H)⁺ 428 N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 460 (M + H)⁺ 429 N-{4-[1-(2-methylbenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 456 (M + H)⁺ 430 1-(pyridazin-3-yl)-N-{4-[1-(1,3-thiazol-4-ylcarbonyl) (ESI(+)) piperidin-4-yl]phenyl}azetidine-3-carboxamide m/e 449 (M + H)⁺ 431 1-(pyridazin-3-yl)-N-{4-[1-(1,3-thiazol-5-ylcarbonyl) (ESI(+)) piperidin-4-yl]phenyl}azetidine-3-carboxamide m/e 449 (M + H)⁺ 432 N-{4-[1-(ethoxyacetyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 424 (M + H)⁺ 433 1-(pyridazin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl) (ESI(+)) piperidin-4-yl]phenyl}azetidine-3-carboxamide m/e 462 (M + H)⁺ 434 N-(4-{1-[(6-methylpyridin-3-yl)carbonyl]piperidin- (ESI(+)) 4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 457 (M + H)⁺ 435 N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(pyridazin- (ESI(+)) 3-yl)azetidine-3-carboxamide m/e 442 (M + H)⁺ 436 N-{4-[1-(furan-2-ylcarbonyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 432 (M + H)⁺ 437 N-(4-{1-[(1-methylcyclohexyl)carbonyl]piperidin- (ESI(+)) 4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 462 (M + H)⁺ 438 N-{4-[1-(2-oxopropanoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 408 (M + H)⁺ 439 N-{4-[1-(cyclopentylcarbonyl)piperidin-4-yl] (ESI(+)) phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 434 (M + H)⁺ 440 N-[4-(1-propanoylpiperidin-4-yl)phenyl]-1-(pyridazin- (ESI(+)) 3-yl)azetidine-3-carboxamide m/e 394 (M + H)⁺ 441 N-{4-[1-(4-methylbenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 456 (M + H)⁺

Example 148 N-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide Example 148A 4-(1-isobutyl-1H-pyrazol-4-yl)aniline

A suspension of 4-bromoaniline (406 mg, 2.362 mmol), 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (650 mg, 2.60 mmol), PdCl₂(dppf)-dichloromethane adduct (57.9 mg, 0.071 mmol) and sodium carbonate (526 mg, 4.96 mmol) in a 6:2:1 mixture of tetrahydrofuran/methanol/water (12 ml) was taken through three vacuum/nitrogen purge cycles; and the reaction mixture was heated in an oil bath at 85° C. overnight. The mixture was diluted with ethyl acetate and water; the separated aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with brine, dried with magnesium sulfate, filtered and concentrated. The residue was purified by normal phase chromatography to give the title compound.

Example 148B benzyl 3-((4-(1-isobutyl-1H-pyrazol-4-yl)phenyl)carbamoyl)azetidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting 4-(1-isobutyl-1H-pyrazol-4-yl)aniline for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate.

Example 148C N-(4-(1-isobutyl-1H-pyrazol-4-yl)phenyl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1B, substituting benzyl 3-((4-(1-isobutyl-1H-pyrazol-4-yl)phenyl)carbamoyl)azetidine-1-carboxylate for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 148D N-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1C, substituting 4-bromopyridazine for 3-bromopyridine and N-(4-(1-isobutyl-1H-pyrazol-4-yl)phenyl)azetidine-3-carboxamide for tert-butyl 4-(4-(azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.10 (s, 1H), 8.61 (d, J=6.0 Hz, 1H), 8.51 (d, J=3.0 Hz, 1H), 8.08 (s, 1H), 7.81 (s, 1H), 7.64-7.56 (m, 2H), 7.55-7.48 (m, 2H), 6.55 (dd, J=6.0, 3.0 Hz, 1H), 4.31-3.96 (m, 4H), 3.91 (d, J=7.1 Hz, 2H), 3.74 (s, 1H), 2.12 (dd, J=13.3, 6.5 Hz, 1H), 0.86 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 377 (M+H)⁺.

Example 199 N-(4-{[1-(4-fluorobenzoyl)azetidin-3-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1, substituting tert-butyl 4-(4-aminophenoxyl)azetidinyl-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate in Example 1A, 4-bromopyridazine for 3-bromopyridyl in Example 1C and 4-fluorobenzoic acid for 2-(tetrahydro-2H-pyran-4-yl)acetic acid in Example 1E. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.01 (s, 1H), 8.67-8.44 (m, 1H), 7.83-7.63 (m, 2H), 7.62-7.43 (m, 2H), 7.43-7.18 (m, 2H), 6.90-6.77 (m, 2H), 6.55 (dd, J=6.1, 3.1 Hz, 1H), 5.13-4.94 (m, 1H), 4.61 (d, J=52.0 Hz, 2H), 4.36-4.04 (m, 4H), 3.99 (s, 1H), 3.70 (ddt, J=33.0, 30.2, 15.0 Hz, 1H), 1.21 (t, J=15.0 Hz, 3H); MS (ESI(+)) m/e 448 (M+H)⁺.

The following Examples were prepared essentially as described in Example 1, substituting the appropriate amine for tert-butyl 4-(4-aminophenoxy)piperidine-1-carboxylate in Example 1A, 4-bromopyridazine for 3-bromopyridyl in Example 1C and the appropriate carboxylic acid for 2-(tetrahydro-2H-pyran-4-yl)acetic acid in Example 1E. Some products were purified by flash chromatography while others were purified by reverse-phase HPLC. Accordingly, some Examples were isolated as trifluoroacetic acid salts.

TABLE 8 Ex Name MS 200 N-(4-{[1-(2,4-difluorobenzoyl)azetidin-3-yl]oxy}phenyl)- (ESI(+)) 1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 466 (M + H)⁺ 201 N-[4-({1-[difluoro(phenyl)acetyl]azetidin-3-yl}oxy) (ESI(+)) phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 480 (M + H)⁺ 202 N-[4-({1-[(4,4-difluorocyclohexyl)carbonyl]azetidin-3- (ESI(+)) yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 472 (M + H)⁺ 203 N-[4-({1-[(4-fluorophenyl)acetyl]azetidin-3-yl}oxy) (ESI(+)) phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 462 (M + H)⁺ 205 1-(pyridazin-4-yl)-N-[4-({1-[4-(trifluoromethyl) (ESI(+)) benzoyl]azetidin-3-yl}oxy)phenyl]azetidine-3-carboxamide m/e 498 (M + H)⁺ 206 N-{4-[(1-benzoylazetidin-3-yl)oxy]phenyl}-1-(pyridazin- (ESI(+)) 4-yl)azetidine-3-carboxamide m/e 430 (M + H)⁺ 207 N-(4-{[1-(2-hydroxy-2-methylpropanoyl)azetidin-3- (ESI(+)) yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 412 (M + H)⁺ 208 1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydrofuran-3- (ESI(+)) ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-3- m/e 424 carboxamide (M + H)⁺ 209 N-(4-{[1-(furan-3-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-1- (ESI(+)) (pyridazin-4-yl)azetidine-3-carboxamide m/e 420 (M + H)⁺ 210 N-{4-[(1-pentanoylazetidin-3-yl)oxy]phenyl}-1-(pyridazin- (ESI(+)) 4-yl)azetidine-3-carboxamide m/e 410 (M + H)⁺ 254 N-(4-{[1-(3,3-dimethylbutanoyl)azetidin-3-yl]oxy}phenyl)- (ESI(+)) 1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 424 (M + H)⁺ 255 N-(4-{[1-(cyclohexylcarbonyl)azetidin-3-yl]oxy}phenyl)- (ESI(+)) 1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 436 (M + H)⁺ 256 1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4- (ESI(+)) ylacetyl)azetidin-3-yl]oxy}phenyl)azetidine-3-carboxamide m/e 452 (M + H)⁺ 257 N-[4-({1-[(2-methylcyclopropyl)carbonyl]azetidin-3- (ESI(+)) yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 408 (M + H)⁺ 258 1-(pyridazin-4-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl) (ESI(+)) azetidin-3-yl]oxy}phenyl)azetidine-3-carboxamide m/e 436 (M + H)⁺ 259 N-(4-{[1-(cyclopentylcarbonyl)azetidin-3-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 422 (M + H)⁺ 260 N-(4-{[1-(3,3-dimethylbutanoyl)piperidin-4-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 452 (M + H)⁺ 261 N-(4-{[1-(cyclobutylcarbonyl)azetidin-3-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 408 (M + H)⁺ 262 1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydrofuran-2- (ESI(+)) ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-3- m/e 424 carboxamide (M + H)⁺ 263 N-(4-{[1-(4-methylpentanoyl)azetidin-3-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 424 (M + H)⁺ 264 N-(4-{[1-(2-methylpropanoyl)azetidin-3-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 396 (M + H)⁺ 265 N-[4-({1-[(2S)-2-methylbutanoyl]azetidin-3-yl}oxy) (ESI(+)) phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 410 (M + H)⁺ 266 N-(4-{[1-(3-methylbutanoyl)piperidin-4-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 438 (M + H)⁺ 267 N-(4-{[1-(methoxyacetyl)piperidin-4-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 426 (M + H)⁺ 268 1-(pyridazin-4-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl) (ESI(+)) piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide m/e 464 (M + H)⁺ 269 N-[4-({1-[difluoro(phenyl)acetyl]piperidin-4-yl} (ESI(+)) oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 508 (M + H)⁺ 270 N-[4-({1-[(4,4-difluorocyclohexyl)carbonyl]piperidin-4- (ESI(+)) yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 500 (M + H)⁺ 271 N-(4-{[1-(4-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)- (ESI(+)) 1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 476 (M + H)⁺ 272 1-(pyridazin-4-yl)-N-(4-{[1-(1,3-thiazol-4-ylcarbonyl) (ESI(+)) piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide m/e 465 (M + H)⁺ 273 1-(pyridazin-4-yl)-N-{4-[(1-{[4- (ESI(+)) (trifluoromethyl)phenyl]acetyl}piperidin-4-yl)oxy] m/e 540 phenyl}azetidine-3-carboxamide (M + H)⁺ 274 N-(4-{[1-(3,4-difluorobenzoyl)piperidin-4-yl]oxy] (ESI(+)) phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 494 (M + H)⁺ 275 1-(pyridazin-4-yl)-N-{4-[(1-{[4- (ESI(+)) (trifluoromethoxy)phenyl]acetyl}piperidin-4- m/e 556 yl)oxy]phenyl}azetidine-3-carboxamide (M + H)⁺ 276 N-[4-({1-[(4-fluorophenyl)acetyl]piperidin-4-yl}oxy) (ESI(+)) phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 490 (M + H)⁺ 277 N-[4-({1-[(2,4-difluorophenyl)acetyl]piperidin-4-yl} (ESI(+)) oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 508 (M + H)⁺ 278 1-(pyridazin-4-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl) (ESI(+)) piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide m/e 464 (M + H)⁺ 279 N-(4-{[1-(2-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)- (ESI(+)) 1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 492 (M + H)⁺ 280 N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl] (ESI(+)) oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 438 (M + H)⁺ 281 N-(4-{[1-(2-methyl-2-phenylpropanoyl)piperidin- (ESI(+)) 4-yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3- m/e 500 carboxamide (M + H)⁺ 282 N-{4-[(1-acetylpiperidin-4-yl)oxy]phenyl}-1- (ESI(+)) (pyridazin-4-yl)azetidine-3-carboxamide m/e 396 (M + H)⁺ 283 1-(pyridazin-4-yl)-N-(4-{[1-(1,3-thiazol-2- (ESI(+)) ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine- m/e 465 3-carboxamide (M + H)⁺ 284 N-(4-{[1-(2,4-difluorobenzoyl)piperidin-4-yl] (ESI(+)) oxy]phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 494 (M + H)⁺ 285 1-(pyridazin-4-yl)-N-[4-({1-[3-(trifluoromethyl) (ESI(+)) benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3- m/e 526 carboxamide (M + H)⁺ 286 N-(4-{[1-(3-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)- (ESI(+)) 1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 476 (M + H)⁺ 287 1-(pyridazin-4-yl)-N-[4-({1-[4-(trifluoromethyl) (ESI(+)) benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3- m/e 526 carboxamide (M + H)⁺ 288 N-[4-({1-[(3-fluorophenyl)acetyl]piperidin-4-yl} (ESI(+)) oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 490 (M + H)⁺ 289 N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 476 (M + H)⁺ 290 1-(pyridazin-4-yl)-N-[4-({1-[4-(trifluoromethoxy) (ESI(+)) benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3- m/e 542 carboxamide (M + H)⁺ 291 N-[4-({1-[(3,5-difluorophenyl)acetyl]piperidin-4-yl} (ESI(+)) oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 508 (M + H)⁺ 292 1-(pyridazin-4-yl)-N-[4-({1-[3-(trifluoromethoxy) (ESI(+)) benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3- m/e 542 carboxamide (M + H)⁺ 293 N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 436 (M + H)⁺ 294 N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 424 (M + H)⁺ 295 N-(4-{[1-(3-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)- (ESI(+)) 1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 492 (M + H)⁺ 296 1-(pyridazin-4-yl)-N-(4-{[1-(pyridin-2-ylcarbonyl) (ESI(+)) piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide m/e 459 (M + H)⁺ 297 N-(4-{[1-(4-chlorobenzoyl)piperidin-4-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 492 (M + H)⁺ 298 1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydrofuran-3- (ESI(+)) ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3- m/e 452 carboxamide (M + H)⁺ 299 N-(4-{[1-(3,5-difluorobenzoyl)piperidin-4-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 494 (M + H)⁺ 300 N-(4-{[1-(2,2-dimethylbutanoyl)piperidin-4-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 452 (M + H)⁺ 301 N-(4-{[1-(cyclopropylcarbonyl)piperidin-4-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 422 (M + H)⁺ 302 1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydrofuran-2- (ESI(+)) ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3- m/e 452 carboxamide (M + H)⁺ 303 1-(pyridazin-4-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl) (ESI(+)) piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide m/e 464 (M + H)⁺ 304 N-[4-({1-[(5-methylthiophen-2-yl)carbonyl]piperidin- (ESI(+)) 4-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3- m/e 478 carboxamide (M + H)⁺ 305 1-(pyridazin-4-yl)-N-{4-[(1-{[3- (ESI(+)) (trifluoromethyl)phenyl]acetyl}piperidin-4-yl)oxy] m/e 540 phenyl}azetidine-3-carboxamide (M + H)⁺ 306 1-(pyridazin-4-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4- (ESI(+)) ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3- m/e 466 carboxamide (M + H)⁺ 307 N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy) (ESI(+)) phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 438 (M + H)⁺ 308 N-[4-({1-[(2-fluorophenyl)acetyl]piperidin-4-yl}oxy) (ESI(+)) phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 490 (M + H)⁺ 396 N-(4-{[(3R)-1-(4-fluorobenzoyl)pyrrolidin-3-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 462 (M + H)⁺ 442 N-(4-{[(3R)-1-(2-chlorobenzoyl)pyrrolidin-3-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 478 (M + H)⁺ 443 1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(1,3-thiazol-2- (ESI(+)) ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3- m/e 451 carboxamide (M + H)⁺ 444 N-(4-{[(3R)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 422 (M + H)⁺ 445 N-[4-({(3R)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl} (ESI(+)) oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 424 (M + H)⁺ 446 1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(tetrahydro-2H-pyran-4- (ESI(+)) ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3- m/e 452 carboxamide (M + H)⁺ 447 1-(pyridazin-4-yl)-N-(4-{[(3R)-1-{[4- (ESI(+)) (trifluoromethoxy)phenyl]acetyl}pyrrolidin-3- m/e 542 yl]oxy}phenyl)azetidine-3-carboxamide (M + H)⁺ 448 1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(thiophen-3-ylcarbonyl) (ESI(+)) pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide m/e 450 (M + H)⁺ 449 N-[4-({(3R)-1-[(4-fluorophenyl)acetyl]pyrrolidin-3-yl} (ESI(+)) oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 476 (M + H)⁺ 450 N-[4-({(3R)-1-[(3,5-difluorophenyl)acetyl]pyrrolidin-3- (ESI(+)) yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 494 (M + H)⁺ 451 N-(4-{[(3R)-1-(3,4-difluorobenzoyl)pyrrolidin-3-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 480 (M + H)⁺ 452 N-[4-({(3R)-1-[(3-fluorophenyl)acetyl]pyrrolidin-3-yl} (ESI(+)) oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 476 (M + H)⁺ 453 1-(pyridazin-4-yl)-N-[4-({(3R)-1-[3- (ESI(+)) (trifluoromethyl)benzoyl]pyrrolidin-3-yl}oxy)phenyl] m/e 512 azetidine-3-carboxamide (M + H)⁺ 454 N-[4-({(3R)-1-[(2,4-difluorophenyl)acetyl]pyrrolidin-3- (ESI(+)) yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 494 (M + H)⁺ 455 1-(pyridazin-4-yl)-N-(4-{[(3R)-1-{[4- (ESI(+)) (trifluoromethyl)phenyl]acetyl}pyrrolidin-3- m/e 526 yl]oxy}phenyl)azetidine-3-carboxamide (M + H)⁺ 456 1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(1,3-thiazol-4- (ESI(+)) ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3- m/e 451 carboxamide (M + H)⁺ 457 1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(tetrahydrofuran-2- (ESI(+)) ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3- m/e 438 carboxamide (M + H)⁺ 458 N-[4-({(3R)-1-[(5-methylthiophen-2-yl)carbonyl]pyrrolidin- (ESI(+)) 3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 464 (M + H)⁺ 459 N-[4-({(3R)-1-[(2-fluorophenyl)acetyl]pyrrolidin-3-yl} (ESI(+)) oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 476 (M + H)⁺ 460 N-(4-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 408 (M + H)⁺ 461 1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(tetrahydrofuran-3- (ESI(+)) ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3- m/e 438 carboxamide (M + H)⁺ 462 1-(pyridazin-4-yl)-N[4-({(3R)-1-[3- (ESI(+)) (trifluoromethoxy)benzoyl]pyrrolidin-3-yl}oxy)phenyl] m/e 528 azetidine-3-carboxamide (M + H)⁺ 463 1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(pyridin-2-ylcarbonyl) (ESI(+)) pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide m/e 445 (M + H)⁺ 464 N-(4-{[(3R)-1-(3-chlorobenzoyl)pyrrolidin-3-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 478 (M + H)⁺ 465 N-(4-{[(3R)-1-(4-chlorobenzoyl)pyrrolidin-3-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 478 (M + H)⁺ 466 N-(4-{[(3R)-1-(2-methyl-2-phenylpropanoyl)pyrrolidin-3- (ESI(+)) yl]oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 486 (M + H)⁺ 467 N-(4-{[(3R)-1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 480 (M + H)⁺ 468 N-(4-{[(3R)-1-(methoxyacetyl)pyrrolidin-3-yl]oxy}phenyl)- (ESI(+)) 1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 412 (M + H)⁺ 469 1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(thiophen-2- (ESI(+)) ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3- m/e 450 carboxamide (M + H)⁺ 470 1-(pyridazin-4-yl)-N-(4-{[(3R)-1-{[3- (ESI(+)) (trifluoromethyl)phenyl]acetyl}pyrrolidin-3- m/e 526 yl]oxy}phenyl)azetidine-3-carboxamide (M + H)⁺ 471 N-(4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3-yl] (ESI(+)) oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 410 (M + H)⁺ 472 N-(4-{[(3R)-1-(2-fluorobenzoyl)pyrrolidin-3-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 462 (M + H)⁺ 473 N-(4-{R3R)-1-(2,2-dimethylbutanoyl)pyrrolidin-3-yl] (ESI(+)) oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 438 (M + H)⁺ 474 N-(4-{[(3R)-1-(3,5-difluorobenzoyl)pyrrolidin-3-yl] (ESI(+)) oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 480 (M + H)⁺ 475 1-(pyridazin-4-yl)-N[4-({(3R)-1-[4- (ESI(+)) (trifluoromethyl)benzoyl]pyrrolidin-3-yl}oxy)phenyl] m/e 512 azetidine-3-carboxamide (M + H)⁺ 476 N-(4-{[(3R)-1-(3-fluorobenzoyl)pyrrolidin-3-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 462 (M + H)⁺ 477 1-(pyridazin-4-yl)-N[4-({(3R)-1-[4- (ESI(+)) (trifluoromethoxy)benzoyl]pyrrolidin-3-yl}oxy)phenyl] m/e 528 azetidine-3-carboxamide (M + H)⁺ 478 N-(4-{[(3R)-1-(3-methylbutanoyl)pyrrolidin-3-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 424 (M + H)⁺ 479 1-(pyridazin-4-yl)-N-(4-{[(3R)-1-(3,3,3- (ESI(+)) trifluoropropanoyl)pyrrolidin-3-yl]oxy}phenyl)azetidine- m/e 450 3-carboxamide (M + H)⁺ 480 N-[4-({(3R)-1-[difluoro(phenyl)acetyl]pyrrolidin-3-yl} (ESI(+)) oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 494 (M + H)⁺ 481 N-(4-{[(3R)-1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl] (ESI(+)) oxy}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 424 (M + H)⁺ 482 N-[4-({(3R)-1-[(4,4-difluorocyclohexyl)carbonyl]pyrrolidin- (ESI(+)) 3-yl}oxy)phenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide m/e 486 (M + H)⁺

Example 204 (3S)—N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1, substituting (S)-1-((benzyloxy)carbonyl)pyrrolidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid acid and tert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate in Example 1A, and cyclopentylbenzoic acid for 2-(tetrahydro-2H-pyran-4-yl)acetic acid in Example 1E. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.03 (s, 1H), 7.95 (d, J=2.8 Hz, 1H), 7.85 (dd, J=4.6, 1.2 Hz, 1H), 7.55 (t, J=10.1 Hz, 2H), 7.16 (dd, J=8.3, 4.3 Hz, 3H), 6.92 (ddd, J=8.4, 2.9, 1.3 Hz, 1H), 4.54 (d, J=12.7 Hz, 1H), 3.98 (d, J=13.7 Hz, 1H), 3.64-3.48 (m, 1H), 3.48-3.38 (m, 1H), 3.22-2.87 (m, 2H), 2.68 (dd, J=24.3, 12.3 Hz, 1H), 2.41-2.01 (m, 6H), 1.77 (s, 4H), 1.68-1.04 (m, 9H); MS (ESI(+)) m/e 461 (M+H)⁺.

Example 211 N-(4-{[1-(2-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 147, substituting tert-butyl 4-(4-(azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate for 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate in Example 147A and 2-chlorobenzoic acid for 2-methylpropanoic acid in Example 147D. ¹H NMR (400 MHz, DMSO/D₂O) δ ppm 8.51 (dd, J=4.4, 1.2 Hz, 1H), 7.78-7.66 (m, 1H), 7.55-7.45 (m, 3H), 7.45-7.37 (m, 2H), 7.37-7.28 (m, 2H), 7.01-6.89 (m, 2H), 4.63-4.34 (m, 6H), 4.03-3.86 (m, 1H), 3.86-3.72 (m, 1H), 3.63-3.43 (m, 1H), 3.43-3.31 (m, 1H), 3.26-3.07 (m, 1H), 2.06-1.80 (m, 2H), 1.80-1.53 (m, 2H), 1.28-1.21 (m, 1H); MS (ESI(+)) m/e 492 (M+H)⁺.

The following Examples were prepared essentially as described in Example 147, substituting the appropriate amine in Example 147A and the appropriate carboxylic acid in Example 147D. Some products were purified by flash chromatography while others were purified by reverse-phase HPLC. Accordingly, some Examples were isolated as trifluoroacetic acid salts.

TABLE 9 Ex Name MS 212 N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl} (ESI(+)) oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3- m/e 438 carboxamide (M + H)⁺ 213 1-(pyridazin-3-yl)-N-(4-{[1-(1,3-thiazol-2-ylcarbonyl) (ESI(+)) piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide m/e 465 (M + H)⁺ 214 1-(pyridazin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4- (ESI(+)) ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3- m/e 466 carboxamide (M + H)⁺ 215 N-[4-({1-[difluoro(phenyl)acetyl]piperidin-4-yl}oxy) (ESI(+)) phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 508 (M + H)⁺ 216 N-[4-({1-[(4,4-difluorocyclohexyl)carbonyl]piperidin- (ESI(+)) 4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3- m/e 500 carboxamide (M + H)⁺ 217 N-(4-{[1-(2-methyl-2-phenylpropanoyl)piperidin-4- (ESI(+)) yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3- m/e 500 carboxamide (M + H)⁺ 218 1-(pyridazin-3-yl)-N-(4-{[1-(1,3-thiazol-4-ylcarbonyl) (ESI(+)) piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide m/e 465 (M + H)⁺ 219 N-[4-({1-[(5-methylthiophen-2-yl)carbonyl]piperidin- (ESI(+)) 4-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3- m/e 478 carboxamide (M + H)⁺ 220 1-(pyridazin-3-yl)-N-{4-[(1-{[4- (ESI(+)) (trifluoromethyl)phenyl]acetyl}piperidin-4-yl)oxy] m/e 540 phenyl}azetidine-3-carboxamide (M + H)⁺ 221 1-(pyridazin-3-yl)-N-(4-{[1-(tetrahydrofuran-2- (ESI(+)) ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine- m/e 452 3-carboxamide (M + H)⁺ 222 1-(pyridazin-3-yl)-N-[4-({1-[3-(trifluoromethyl) (ESI(+)) benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3- m/e 526 carboxamide (M + H)⁺ 223 1-(pyridazin-3-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl) (ESI(+)) piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide m/e 464 (M + H)⁺ 224 1-(pyridazin-3-yl)-N-[4-({1-[3-(trifluoromethoxy) (ESI(+)) benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3- m/e 542 carboxamide (M + H)⁺ 225 N-(4-{[1-(3-methylbutanoyl)piperidin-4-yl]oxy}phenyl)- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 438 (M + H)⁺ 226 1-(pyridazin-3-yl)-N-(4-{[1-(tetrahydrofuran-3- (ESI(+)) ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-3- m/e 452 carboxamide (M + H)⁺ 227 N-[4-({1-[(3-fluorophenyl)acetyl]piperidin-4-yl}oxy) (ESI(+)) phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 490 (M + H)⁺ 228 N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 476 (M + H)⁺ 229 N-(4-{[1-(2,4-difluorobenzoyl)piperidin-4-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 494 (M + H)⁺ 230 N-(4-{[1-(4-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 476 (M + H)⁺ 231 N-(4-{[1-(3-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 476 (M + H)⁺ 232 N-[4-({1-[(4-fluorophenyl)acetyl]piperidin-4-yl}oxy) (ESI(+)) phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 490 (M + H)⁺ 233 N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 436 (M + H)⁺ 234 N-(4-{[1-(3,4-difluorobenzoyl)piperidin-4-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 494 (M + H)⁺ 235 1-(pyridazin-3-yl)-N-[4-({1-[4-(trifluoromethoxy) (ESI(+)) benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3- m/e 542 carboxamide (M + H)⁺ 236 N-[4-({1-[(2,4-difluorophenyl)acetyl]piperidin-4-yl} (ESI(+)) oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 508 (M + H)⁺ 237 1-(pyridazin-3-yl)-N-[4-({1-[4-(trifluoromethyl) (ESI(+)) benzoyl]piperidin-4-yl}oxy)phenyl]azetidine-3- m/e 526 carboxamide (M + H)⁺ 238 1-(pyridazin-3-yl)-N-{4-[(1-{[4- (ESI(+)) (trifluoromethoxy)phenyl]acetyl}piperidin-4- m/e 556 yl)oxy]phenyl}azetidine-3-carboxamide (M + H)⁺ 239 N-[4-({1-[(3,5-difluorophenyl)acetyl]piperidin-4-yl} (ESI(+)) oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3- m/e 508 carboxamide (M + H)⁺ 240 1-(pyridazin-3-yl)-N-{4-[(1-{[3- (ESI(+)) (trifluoromethyl)phenyl]acetyl}piperidin-4-yl)oxy] m/e 540 phenyl}azetidine-3-carboxamide (M + H)⁺ 241 N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 438 (M + H)⁺ 242 1-(pyridazin-3-yl)-N-(4-{[1-(pyridin-2-ylcarbonyl) (ESI(+)) piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide m/e 459 (M + H)⁺ 243 N-(4-{[1-(3,5-difluorobenzoyl)piperidin-4-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 494 (M + H)⁺ 244 -{4-[(1-acetylpiperidin-4-yl)oxy]phenyl}-1-(pyridazin- (ESI(+)) 3-yl)azetidine-3-carboxamide m/e 396 (M + H)⁺ 245 N-(4-{[1-(4-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 492 (M + H)⁺ 246 N-(4-{[1-(methoxyacetyl)piperidin-4-yl]oxy}phenyl)- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 426 (M + H)⁺ 247 N-[4-({1-[(2-fluorophenyl)acetyl]piperidin-4-yl}oxy) (ESI(+)) phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 490 (M + H)⁺ 248 N-(4-{[1-(2,2-dimethylbutanoyl)piperidin-4-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 452 (M + H)⁺ 249 1-(pyridazin-3-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl) (ESI(+)) piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide m/e 464 (M + H)⁺ 250 N-(4-{[1-(3-chlorobenzoyl)piperidin-4-yl]oxy}phenyl)- (ESI(+)) 1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 492 (M + H)⁺ 251 N-(4-{[1-(cyclopropylcarbonyl)piperidin-4-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 422 (M + H)⁺ 252 1-(pyridazin-3-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl) (ESI(+)) piperidin-4-yl]oxy}phenyl)azetidine-3-carboxamide m/e 464 (M + H)⁺ 253 N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 424 (M + H)⁺ 483 N-(4-{[(3R)-1-(2-chlorobenzoyl)pyrrolidin-3-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 478 (M + H)⁺ 484 1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(1,3-thiazol-2- (ESI(+)) ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3- m/e 451 carboxamide (M + H)⁺ 485 N-(4-{[(3R)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 422 (M + H)⁺ 486 N-[4-({(3R)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl} (ESI(+)) oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 424 (M + H)⁺ 487 1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(tetrahydro-2H-pyran- (ESI(+)) 4-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine- m/e 452 3-carboxamide (M + H)⁺ 488 1-(pyridazin-3-yl)-N-(4-{[(3R)-1-{[4- (ESI(+)) (trifluoromethoxy)phenyl]acetyl}pyrrolidin-3- m/e 542 yl]oxy}phenyl)azetidine-3-carboxamide (M + H)⁺ 489 N-(4-{[(3R)-1-(4-fluorobenzoyl)pyrrolidin-3-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 462 (M + H)⁺ 490 1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(thiophen-3- (ESI(+)) ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine- m/e 450 3-carboxamide (M + H)⁺ 491 N-[4-({(3R)-1-[(4-fluorophenyl)acetyl]pyrrolidin-3- (ESI(+)) yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3- m/e 476 carboxamide (M + H)⁺ 492 N-[4-({(3R)-1-[(3,5-difluorophenyl)acetyl]pyrrolidin-3- (ESI(+)) yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 494 (M + H)⁺ 493 N-(4-{[(3R)-1-(3,4-difluorobenzoyl)pyrrolidin-3-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 480 (M + H)⁺ 494 N-[4-({(3R)-1-[(3-fluorophenyl)acetyl]pyrrolidin-3-yl} (ESI(+)) oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 476 (M + H)⁺ 495 1-(pyridazin-3-yl)-N-[4-({(3R)-1-[3- (ESI(+)) (trifluoromethyl)benzoyl]pyrrolidin-3-yl}oxy)phenyl] m/e 512 azetidine-3-carboxamide (M + H)⁺ 496 N-[4-({(3R)-1-[(2,4-difluorophenyl)acetyl]pyrrolidin-3- (ESI(+)) yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 494 (M + H)⁺ 497 1-(pyridazin-3-yl)-N-(4-{[(3R)-1-{[4- (ESI(+)) (trifluoromethyl)phenyl]acetyl}pyrrolidin-3- m/e 526 yl]oxy}phenyl)azetidine-3-carboxamide (M + H)⁺ 498 1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(1,3-thiazol-4- (ESI(+)) ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3- m/e 451 carboxamide (M + H)⁺ 499 1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(tetrahydrofuran-2- (ESI(+)) ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3- m/e 438 carboxamide (M + H)⁺ 500 N-[4-({(3R)-1-[(5-methylthiophen-2-yl)carbonyl] (ESI(+)) pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine- m/e 464 3-carboxamide (M + H)⁺ 501 N-[4-({(3R)-1-[(2-fluorophenyl)acetyl]pyrrolidin-3-yl} (ESI(+)) oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 476 (M + H)⁺ 502 N-(4-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl] (ESI(+)) oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 408 (M + H)⁺ 503 1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(tetrahydrofuran-3- (ESI(+)) ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3- m/e 438 carboxamide (M + H)⁺ 504 1-(pyridazin-3-yl)-N-[4-({(3R)-1-[3- (ESI(+)) (trifluoromethoxy)benzoyl]pyrrolidin-3-yl}oxy)phenyl] m/e 528 azetidine-3-carboxamide (M + H)⁺ 505 1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(pyridin-2-ylcarbonyl) (ESI(+)) pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide m/e 445 (M + H)⁺ 506 N-(4-{[(3R)-1-(3-chlorobenzoyl)pyrrolidin-3-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 478 (M + H)⁺ 507 N-(4-{[(3R)-1-(4-chlorobenzoyl)pyrrolidin-3-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 478 (M + H)⁺ 508 N-(4-{[(3R)-1-(2-methyl-2-phenylpropanoyl)pyrrolidin-3- (ESI(+)) yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 486 (M + H)⁺ 509 N-(4-{[(3R)-1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 480 (M + H)⁺ 510 N-(4-{[(3R)-1-(methoxyacetyl)pyrrolidin-3-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 412 (M + H)⁺ 511 1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(thiophen-2- (ESI(+)) ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3- m/e 450 carboxamide (M + H)⁺ 512 1-(pyridazin-3-yl)-N-(4-{[(3R)-1-{[3- (ESI(+)) (trifluoromethyl)phenyl]acetyl}pyrrolidin-3- m/e 526 yl]oxy}phenyl)azetidine-3-carboxamide (M + H)⁺ 513 N-(4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3- (ESI(+)) yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3- m/e 410 carboxamide (M + H)⁺ 514 N-(4-{[(3R)-1-(2-fluorobenzoyl)pyrrolidin-3-yl] (ESI(+)) oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3- m/e 462 carboxamide (M + H)⁺ 515 N-(4-{[(3R)-1-(2,2-dimethylbutanoyl)pyrrolidin-3- (ESI(+)) yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3- m/e 438 carboxamide (M + H)⁺ 516 N-(4-{[(3R)-1-(3,5-difluorobenzoyl)pyrrolidin-3- (ESI(+)) yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3- m/e 480 carboxamide (M + H)⁺ 517 1-(pyridazin-3-yl)-N-[4-({(3R)-1-[4- (ESI(+)) (trifluoromethyl)benzoyl]pyrrolidin-3-yl}oxy) m/e 512 phenyl]azetidine-3-carboxamide (M + H)⁺ 518 N-(4-{[(3R)-1-(3-fluorobenzoyl)pyrrolidin-3-yl] (ESI(+)) oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 462 (M + H)⁺ 519 1-(pyridazin-3-yl)-N-[4-({(3R)-1-[4- (ESI(+)) (trifluoromethoxy)benzoyl]pyrrolidin-3-yl}oxy) m/e 528 phenyl]azetidine-3-carboxamide (M + H)⁺ 520 N-(4-{[(3R)-1-(3-methylbutanoyl)pyrrolidin-3-yl] (ESI(+)) oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 424 (M + H)⁺ 521 1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(3,3,3- (ESI(+)) trifluoropropanoyl)pyrrolidin-3-yl]oxy}phenyl) m/e 450 azetidine-3-carboxamide (M + H)⁺ 522 N-[4-({(3R)-1-[difluoro(phenyl)acetyl]pyrrolidin- (ESI(+)) 3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine-3- m/e 494 carboxamide (M + H)⁺ 523 N-(4-{[(3R)-1-(2,2-dimethylpropanoyl)pyrrolidin-3- (ESI(+)) yl]oxy}phenyl)-1-(pyridazin-3-yl)azetidine-3- m/e 424 carboxamide (M + H)⁺ 524 N-[4-({(3R)-1-[(4,4-difluorocyclohexyl)carbonyl] (ESI(+)) pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)azetidine- m/e 486 3-carboxamide (M + H)⁺

Example 309 5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]furan-2-carboxamide Example 309A tert-butyl (1-(6-chloropyridazin-3-yl)azetidin-3-yl)carbamate

tert-Butyl azetidin-3-ylcarbamate (500 mg, 2.90 mmol) and 3,6-dichloropyridazine (454 mg, 3.05 mmol) were combined in DMSO (5 mL) and N-ethyl-N-isopropylpropan-2-amine (563 mg, 4.35 mmol), and the mixture was heated overnight at 100° C. The mixture was cooled to room temperature and diluted with water. Filtration provided the title compound.

Example 309B tert-butyl (1-(pyridazin-3-yl)azetidin-3-yl)carbamate

A mixture of tert-butyl 1-(6-chloropyridizan-3-yl)azetidin-3-ylcarbamate (413 mg, 1.45 mmol), 1,4-cyclohexadiene (1.10 mL, 11.6 mmol) and triethylamine (0.61 mL, 1.45 mmol) was purged with nitrogen and 5% palladium on carbon (20 mg) was added. The reaction mixture was heated to 80° C. overnight, cooled to room temperature and filtered through diatomaceous earth, rinsing with methanol. Concentration provided the title compound.

Example 309C 1-(pyridazin-3-yl)azetidin-3-amine

Tert-butyl 1-(pyridazin-3-yl)azetidin-3-ylcarbamate.triethylamine hydrochloride (200 mg, 0.516 mmol) was dissolved in methanol (1.5 mL) and a 4N solution of HCl in dioxane (1.5 mL, 6.00 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 1 hour then concentrated to dryness to give the title compound.

Example 309D 5-(1-isobutyl-1H-pyrazol-4-yl)furan-2-carboxylic acid

The title compound was prepared as described as described in Example 148A, substituting 5-bromofuran-2-carboxylic acid for 4-bromoaniline.

Example 309E 5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]furan-2-carboxamide

The title compound was prepared as described in Example 1A, substituting 1-(pyridazin-3-yl)azetidin-3-amine for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 5-(1-isobutyl-1H-pyrazol-4-yl)furan-2-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 8.83 (d, J=7.5 Hz, 1H), 8.57 (dd, J=4.5, 1.3 Hz, 1H), 8.15 (d, J=0.7 Hz, 1H), 7.88 (d, J=0.7 Hz, 1H), 7.39 (dd, J=8.9, 4.5 Hz, 1H), 7.16 (d, J=3.5 Hz, 1H), 6.84 (dd, J=8.9, 1.4 Hz, 1H), 6.64 (d, J=3.5 Hz, 1H), 4.97-4.84 (m, 1H), 4.38 (t, J=8.1 Hz, 2H), 4.06 (dd, J=8.6, 5.7 Hz, 2H), 3.95 (d, J=7.2 Hz, 2H), 2.21-2.05 (m, 1H), 0.85 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 367 (M+H)⁺.

Example 310 (3S)—N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 147, substituting (S)-tert-butyl 4-(4-(pyrrolidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate in Example 147A. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.06 (s, 1H), 8.48 (dd, J=4.4, 1.2 Hz, 1H), 7.54 (d, J=8.5 Hz, 2H), 7.43-7.25 (m, 1H), 7.18 (d, J=8.6 Hz, 2H), 6.87 (dd, J=9.2, 1.2 Hz, 1H), 4.64-4.48 (m, 1H), 4.15-3.97 (m, 1H), 3.76 (dd, J=10.4, 8.0 Hz, 1H), 3.69-3.54 (m, 2H), 3.54-3.38 (m, 1H), 3.20-3.03 (m, 1H), 3.02-2.83 (m, 2H), 2.79-2.64 (m, 1H), 2.64-2.52 (m, 1H), 2.37-2.13 (m, 2H), 1.90-1.68 (m, 2H), 1.59-1.29 (m, 2H), 0.99 (dt, J=14.5, 7.0 Hz, 6H); MS (ESI(+)) m/e 422 (M+H)⁺.

Example 311 (3S)—N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 147, substituting (S)-tert-butyl 4-(4-(pyrrolidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate in Example 147A and benzoic acid for 2-methylpropanoic acid in Example 147D. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.06 (s, 1H), 8.48 (dd, J=4.4, 1.3 Hz, 1H), 7.55 (d, J=8.6 Hz, 1H), 7.51-7.39 (m, 5H), 7.34 (dd, J=9.1, 4.5 Hz, 1H), 7.25-7.19 (m, 2H), 6.87 (dd, J=9.1, 1.3 Hz, 1H), 4.65-4.48 (m, 1H), 3.84-3.53 (m, 4H), 3.48 (dt, J=10.2, 7.4 Hz, 1H), 3.22-2.69 (m, 3H), 2.36-2.13 (m, 2H), 1.98-1.48 (m, 4H); MS (ESI(+)) m/e 456 (M+H)⁺.

Example 312 (3S)-1-(pyridazin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 147, substituting (S)-tert-butyl 4-(4-(pyrrolidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate in Example 147A and tetrahydro-2H-pyran-4-ylacetic acid for 2-methylpropanoic acid in Example 147D. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.06 (s, 1H), 8.48 (dd, J=4.4, 1.2 Hz, 1H), 7.54 (d, J=8.6 Hz, 2H), 7.39-7.27 (m, 1H), 7.17 (d, J=8.6 Hz, 2H), 6.87 (dd, J=9.2, 1.2 Hz, 1H), 4.65-4.45 (m, 1H), 4.07-3.92 (m, 1H), 3.89-3.68 (m, 3H), 3.68-3.54 (m, 2H), 3.54-3.39 (m, 1H), 3.22-2.93 (m, 2H), 2.80-2.65 (m, 1H), 2.64-2.52 (m, 1H), 2.38-2.13 (m, 4H), 2.00-1.84 (m, 1H), 1.80 (dt, J=27.7, 7.7 Hz, 2H), 1.68-1.14 (m, 7H); MS (ESI(+)) m/e 478 (M+H)⁺.

Example 313 (3S)—N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 147, substituting (S)-tert-butyl 4-(4-(pyrrolidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate in Example 147A and 2,2-dimethylpropanoic acid for 2-methylpropanoic acid in Example 147D. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.05 (s, 1H), 8.47 (dd, J=4.4, 1.0 Hz, 1H), 7.52 (d, J=8.5 Hz, 2H), 7.32 (dd, J=9.1, 4.5 Hz, 1H), 7.16 (d, J=8.5 Hz, 2H), 6.86 (dd, J=9.2, 1.0 Hz, 1H), 4.39 (d, J=13.2 Hz, 2H), 3.75 (dd, J=10.4, 8.0 Hz, 1H), 3.69-3.54 (m, 2H), 3.46 (dt, J=10.1, 7.5 Hz, 1H), 3.27 (dd, J=14.8, 7.4 Hz, 1H), 2.96 (dd, J=12.8, 7.0 Hz, 1H), 2.84 (dd, J=22.1, 9.6 Hz, 2H), 2.78-2.64 (m, 1H), 2.27 (dt, J=7.1, 5.0 Hz, 1H), 2.18 (ddd, J=14.3, 11.6, 7.3 Hz, 1H), 1.77 (d, J=11.3 Hz, 2H), 1.54-1.31 (m, 3H), 1.18 (d, J=16.8 Hz, 9H); MS (ESI(+)) m/e 436 (M+H)⁺.

The following Examples were essentially prepared as described in Example 313, substituting the appropriate carboxylic acid for 2,2-dimethylpropanoic acid

TABLE 10 Ex Name MS 630 (3S)-1-(pyridazin-3-yl)-N-{4-[1-(1,3-thiazol-5- (ESI(+)) ylcarbonyl)piperidin-4-yl]phenyl}pyrrolidine-3- m/e 463 carboxamide (M + H)⁺ 631 (3S)-N-{4-[1-(4-methylbenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 470 (M + H)⁺ 632 (3S)-N-(4-{1-[(25)-2-phenylbutanoyl]piperidin-4-yl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 498 (M + H)⁺ 633 (3S)-N-(4-{1-[(2S)-2-methoxy-2-phenylacetyl]piperidin- (ESI(+)) 4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3- m/e 500 carboxamide (M + H)⁺ 634 (3S)-N-(4-{1-[(2R)-2-methoxy-2-phenylacetyl]piperidin- (ESI(+)) 4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3- m/e 500 carboxamide (M + H)⁺ 635 (3S)-N-{4-[1-(ethoxyacetyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 438 (M + H)⁺ 636 (3S)-N-(4-{1-[(4-methylphenoxy)acetyl]piperidin-4- (ESI(+)) yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3- m/e 500 carboxamide (M + H)⁺ 637 (3S)-N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 474 (M + H)⁺ 638 (3S)-1-(pyridazin-3-yl)-N-{4-[1-(tetrahydrofuran-3- (ESI(+)) ylcarbonyl)piperidin-4-yl]phenyl}pyrrolidine-3- m/e 450 carboxamide (M + H)⁺ 639 (3S)-N-{4-[1-(naphthalen-1-ylcarbonyl)piperidin-4- (ESI(+)) yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 506 (M + H)⁺ 640 (3S)-N-(4-{1-[(2,6-dichlorophenyl)acetyl]piperidin-4- (ESI(+)) yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 538 (M + H)⁺ 641 (3S)-N-{4-[1-(naphthalen-1-ylacetyl)piperidin-4-yl] (ESI(+)) phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 520 (M + H)⁺ 642 (3S)-1-(pyridazin-3-yl)-N-(4-{1-[4-(thiophen-2- (ESI(+)) yl)butanoyl]piperidin-4-yl}phenyl)pyrrolidine-3- m/e 504 carboxamide (M + H)⁺ 643 (3S)-N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 434 (M + H)⁺ 644 (3S)-N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 462 (M + H)⁺ 645 (3S)-N-{4-[1-(2,5-difluorobenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 492 (M + H)⁺ 646 (3S)-N-{4-[1-(naphthalen-2-ylacetyl)piperidin-4-yl] (ESI(+)) phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 520 (M + H)⁺ 647 (3S)-N-(4-{1-[3-(phenylsulfonyl)propanoyl]piperidin- (ESI(+)) 4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3- m/e 548 carboxamide (M + H)⁺ 648 (3S)-1-(pyridazin-3-yl)-N-[4-(1-{[3- (ESI(+)) (trifluoromethyl)phenyl]acetyl}piperidin-4-yl)phenyl] m/e 538 pyrrolidine-3-carboxamide (M + H)⁺ 649 (3S)-N-{4-[1-(furan-2-ylcarbonyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 446 (M + H)⁺ 650 (3S)-N-{4-[1-(N-benzoylglycyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 513 (M + H)⁺ 651 (3S)-N-(4-{1-[(2,4-dichlorophenyl)acetyl]piperidin-4-yl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 538 (M + H)⁺ 652 (3S)-N-{4-[1-(2-methylbenzoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 470 (M + H)⁺ 653 (3S)-1-(pyridazin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl) (ESI(+)) piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide m/e 476 (M + H)⁺ 654 (3S)-N-(4-{1-[(1-methylcyclohexyl)carbonyl]piperidin-4- (ESI(+)) yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 476 (M + H)⁺ 655 (3S)-1-(pyridazin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl) (ESI(+)) piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide m/e 462 (M + H)⁺ 656 (3S)-N-(4-{1-[(6-methylpyridin-3-yl)carbonyl]piperidin-4- (ESI(+)) yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 471 (M + H)⁺ 657 (3S)-N-(4-{1-[(3-chlorophenyl)acetyl]piperidin-4-yl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 504 (M + H)⁺ 658 (3S)-N-[4-(1-propanoylpiperidin-4-yl)phenyl]-1-(pyridazin- (ESI(+)) 3-yl)pyrrolidine-3-carboxamide m/e 408 (M + H)⁺ 659 (3S)-N-{4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 492 (M + H)⁺ 660 (3S)-N-{4-[1-(cyclopentylcarbonyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 448 (M + H)⁺ 661 (3S)-1-(pyridazin-3-yl)-N-{4-[1-(tetrahydrofuran-2- (ESI(+)) ylcarbonyl)piperidin-4-yl]phenyl}pyrrolidine-3- m/e 450 carboxamide (M + H)⁺ 662 (3S)-N-{4-[1-(cyclopropylcarbonyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 420 (M + H)⁺ 663 (3S)-N-{4-[1-(4-chlorobenzoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 490 (M + H)⁺ 669 (3S)-N-{4-[1-(2-chlorobenzoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 490 (M + H)⁺ 670 (3S)-N-{4-[1-(2-methylpentanoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 450 (M + H)⁺ 671 (3S)-N-{4-[1-(4-methylpentanoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 450 (M + H)⁺ 672 (3S)-N-{4-[1-(2,4-dimethylbenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 484 (M + H)⁺ 673 (3S)-N-[4-(1-heptanoylpiperidin-4-yl)phenyl]-1-(pyridazin- (ESI(+)) 3-yl)pyrrolidine-3-carboxamide m/e 464 (M + H)⁺ 674 (3S)-N-{4-[1-(2,4-dichlorobenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 524 (M + H)⁺ 675 (3S)-N-(4-{1-[(4-fluorophenyl)acetyl]piperidin-4-yl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 488 (M + H)⁺ 676 (3S)-N-{4-[1-(2,3-difluorobenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 492 (M + H)⁺ 677 (3S)-N-{4-[1-(3-methylbenzoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 470 (M + H)⁺ 678 (3S)-N-[4-(1-hexanoylpiperidin-4-yl)phenyl]-1-(pyridazin- (ESI(+)) 3-yl)pyrrolidine-3-carboxamide m/e 450 (M + H)⁺ 679 (3S)-N-(4-{1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4- (ESI(+)) yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 476 (M + H)⁺ 680 (3S)-N-{4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 450 (M + H)⁺ 681 (3S)-N-[4-(1-butanoylpiperidin-4-yl)phenyl]-1-(pyridazin-3- (ESI(+)) yl)pyrrolidine-3-carboxamide m/e 422 (M + H)⁺ 682 (3S)-N-{4-[1-(3-methylpentanoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 450 (M + H)⁺ 683 (3S)-N-(4-{1-[(3,5-dimethylphenyl)acetyl]piperidin-4-yl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 498 (M + H)⁺ 684 (3S)-N-{4-[1-(3,5-dichlorobenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 524 (M + H)⁺ 685 (3S)-N-{4-[1-(3-fluoro-2-methylbenzoyl)piperidin-4-yl] (ESI(+)) phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 488 (M + H)⁺ 686 (3S)-N-(4-{1-[(4-chlorophenyl)acetyl]piperidin-4-yl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 504 (M + H)⁺ 687 (3S)-N-{4-[1-(furan-3-ylcarbonyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 446 (M + H)⁺ 688 (3S)-N-{4-[1-(3,4-dimethylbenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 484 (M + H)⁺ 689 (3S)-N-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 474 (M + H)⁺ 690 (3S)-N-(4-{1-[2-chloro-5-(trifluoromethyl)benzoyl] (ESI(+)) piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3- m/e 558 carboxamide (M + H)⁺ 691 (3S)-N-[4-(1-acetylpiperidin-4-yl)phenyl]-1-(pyridazin-3- (ESI(+)) yl)pyrrolidine-3-carboxamide m/e 394 (M + H)⁺ 692 (3S)-N-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 492 (M + H)⁺ 693 (3S)-N-{4-[1-(3,5-dimethylbenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 484 (M + H)⁺ 694 (3S)-N-{4-[1-(3-ethoxypropanoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 452 (M + H)⁺ 695 (3S)-N-{4-[1-(2,5-dichlorobenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 524 (M + H)⁺ 696 (3S)-N-{4-[1-(2,5-dimethylbenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 484 (M + H)⁺ 697 (3S)-N-{4-[1-(5-fluoro-2-methylbenzoyl)piperidin-4-yl] (ESI(+)) phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 488 (M + H)⁺ 698 (3S)-N-{4-[1-(diphenylacetyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 546 (M + H)⁺ 699 (3S)-1-(pyridazin-3-yl)-N-(4-{1-[4- (ESI(+)) (trifluoromethyl)benzoyl]piperidin-4-yl}phenyl)pyrrolidine- m/e 524 3-carboxamide (M + H)⁺ 700 (3S)-N-{4-[1-(pent-4-enoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 434 (M + H)⁺ 701 (3S)-1-(pyridazin-3-yl)-N-(4-{1-[3- (ESI(+)) (trifluoromethoxy)benzoyl]piperidin-4-yl}phenyl) m/e 540 pyrrolidine-3-carboxamide (M + H)⁺ 702 (3S)-N-(4-{1-[(1-phenylcyclopropyl)carbonyl]piperidin-4- (ESI(+)) yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 496 (M + H)⁺ 703 (3S)-N-(4-{1-[2-fluoro-5-(trifluoromethyl)benzoyl]piperidin- (ESI(+)) 4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 542 (M + H)⁺ 704 (3S)-N-{4-[1-(cyclohexylacetyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 476 (M + H)⁺ 705 (3S)-N-{4-[1-(4-methoxybenzoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 486 (M + H)⁺ 706 (3S)-N-{4-[1-(2-methylbutanoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 436 (M + H)⁺ 707 (3S)-N-{4-[1-(2-ethylbutanoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 450 (M + H)⁺ 708 (3S)-N-{4-[1-(4-tert-butylbenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 512 (M + H)⁺ 709 (3S)-N-{4-[1-(3-chlorobenzoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 490 (M + H)⁺ 710 (3S)-N-(4-{1-[(2-fluorophenyl)acetyl]piperidin-4-yl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 488 (M + H)⁺ 711 (3S)-1-(pyridazin-3-yl)-N-(4-{1-[3- (ESI(+)) (trifluoromethyl)benzoyl]piperidin-4-yl}phenyl) m/e 524 pyrrolidine-3-carboxamide (M + H)⁺ 712 (3S)-N-(4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4- (ESI(+)) yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 434 (M + H)⁺ 713 (3S)-N-{4-[1-(pent-4-ynoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 432 (M + H)⁺ 714 (3S)-N-(4-{1-[(3-fluorophenyl)acetyl]piperidin-4-yl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 488 (M + H)⁺ 715 (3S)-N-(4-{1-[3-(methylsulfanyl)propanoyl]piperidin-4-)- (ESI(+)) 1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 454 (M + H)⁺ 716 (3S)-N-(4-{1-[(1-acetylpiperidin-4-yl)carbonyl]piperidin-4- (ESI(+)) yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 505 (M + H)⁺ 717 (3S)-N-{4-[1-(but-3-enoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 420 (M + H)⁺ 718 (3S)-N-{4-[1-(2,2-dimethylbutanoyl)piperidin-4-yl] (ESI(+)) phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 450 (M + H)⁺ 719 (3S)-N-{4-[1-(3-fluoro-4-methylbenzoyl)piperidin-4-yl] (ESI(+)) phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 488 (M + H)⁺ 720 (3S)-N-{4-[1-(3-methoxybenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 486 (M + H)⁺ 721 (3S)-N-(4-{1-[(2-chlorophenyl)acetyl]piperidin-4-yl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 504 (M + H)⁺ 722 (3S)-N-(4-{1-[(2-methoxyethoxy)acetyl]piperidin-4-yl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 468 (M + H)⁺ 723 (3S)-N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl] (ESI(+)) phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 450 (M + H)⁺ 724 (3S)-N-{4-[1-(N-acetyl-L-leucyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 507 (M + H)⁺ 725 (3S)-N-{4-[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 474 (M + H)⁺ 726 (3S)-N-{4-[1-(4-cyanobenzoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 481 (M + H)⁺ 727 (3S)-N-{4-[1-(2-methoxybenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)pyrrolidine-3-carboxamide unie 486 (M + H)⁺ 728 (3S)-N-{4-[1-(2,3-dimethylbenzoyl)piperidin-4-yl] (ESI(+)) phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide unie 484 (M + H)⁺ 729 (3S)-N-(4-{1-[4-(propan-2-yl)benzoyl]piperidin-4-yl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide unie 498 (M + H)⁺ 730 (3S)-N-{4-[1-(cyclohexylcarbonyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)pyrrolidine-3-carboxamide unie 462 (M + H)⁺ 731 (3S)-1-(pyridazin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl) (ESI(+)) piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide unie 462 (M + H)⁺ 732 (3S)-N-{4-[1-(4-hydroxybenzoyl)piperidin-4-yl]phenyl}- (ESI(+)) 1-(pyridazin-3-yl)pyrrolidine-3-carboxamide unie 472 (M + H)⁺ 733 (3S)-N-{4-[1-(3-cyanobenzoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide unie 481 (M + H)⁺ 734 (3S)-1-(pyridazin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl) (ESI(+)) piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide unie 462 (M + H)⁺ 735 (3S)-N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide unie 424 (M + H)⁺ 736 (3S)-N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide unie 436 (M + H)⁺

Example 314 tert-butyl 4-(4-{[1-(pyridazin-3-yl)azetidin-3-yl]carbamoyl}phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting 1-(pyridazin-3-yl)azetidin-3-amine for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 4-(1-(tert-butoxycarbonyl)piperidin-4-yl)benzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ 8.96 (d, J=7.0 Hz, 1H), 8.56 (dd, J=4.6, 1.3 Hz, 1H), 7.82 (d, J=8.3 Hz, 2H), 7.41-7.31 (m, 3H), 6.83 (dd, J=9.0, 1.3 Hz, 1H), 4.96-4.85 (m, 1H), 4.37 (t, J=8.1 Hz, 2H), 4.16-3.97 (m, 4H), 2.88-2.65 (m, 3H), 1.80-1.70 (m, 2H), 1.60-1.43 (m, 2H), 1.41 (s, 9H); MS (ESI(+)) m/e 438 (M+H)⁺.

Example 315 5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide Example 315A 5-(1-isobutyl-1H-pyrazol-4-yl)thiophene-2-carboxylic acid

The title compound was prepared as described as described in Example 148A, substituting 5-bromothiophene-2-carboxylic acid for 4-bromoaniline.

Example 315B 5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting 1-(pyridazin-3-yl)azetidin-3-amine for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 5-(1-isobutyl-1H-pyrazol-4-yl)thiophene-2-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 8.99 (d, J=7.1 Hz, 1H), 8.57 (dd, J=4.5, 1.3 Hz, 1H), 8.14 (d, J=0.8 Hz, 1H), 7.81-7.79 (m, 1H), 7.72 (d, J=3.9 Hz, 1H), 7.39 (dd, J=8.9, 4.5 Hz, 1H), 7.21 (d, J=3.8 Hz, 1H), 6.84 (dd, J=9.0, 1.4 Hz, 1H), 4.92-4.81 (m, 1H), 4.37 (t, J=8.1 Hz, 2H), 4.03 (dd, J=8.6, 5.5 Hz, 2H), 3.92 (d, J=7.1 Hz, 2H), 2.19-2.04 (m, 1H), 0.85 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 383 (M+H)⁺.

Example 564 N-(4-{[1-(3-chlorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide Example 564A tert-butyl 4-((4-(1-((benzyloxy)carbonyl)azetidine-3-carboxamido)phenyl)thio)piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting tert-butyl 4-(4-aminophenylthio)piperidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 564B tert-butyl 4-((4-(1-((benzyloxy)carbonyl)azetidine-3-carboxamido)phenyl)sulfonyl)piperidine-1-carboxylate

To a 20 mL vial was added tert-butyl 4-((4-(1-((benzyloxy)carbonyl)azetidine-3-carboxamido)phenyl)thio)piperidine-1-carboxylate (8.3 g, 15.79 mmol) in dichloromethane (79 ml). The reaction mixture was cooled to ca −20° C. in a methanol dry ice bath treated with m-chloroperbenzoic acid (8.17 g, 47.4 mmol) and was allowed to warm slowly to room temperature. When complete, the reaction mixture was treated with 1N aqueous sodium hydroxide and extracted with dichloromethane. The combined organics were dried with sodium sulfate, filtered and concentrated by rotary evaporation. The residue was purified by regular phase chromatography to give the title compound.

Example 564C tert-butyl 4-(4-(azetidine-3-carboxamido)phenylsulfonyl)piperidine-1-carboxylate

tert-Butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenylsulfonyl)piperidine-1-carboxylate (7.94 g, 14.24 mmol) and ethanol (160 ml) were added to 20% Pd(OH)₂C, wet (1.5 g, 1.089 mmol) in a 250 mL SS pressure bottle and the mixture was stirred for 16 hours at 30 psi and room temperature. The mixture was filtered through a nylon membrane and concentrated to give the title compound.

Example 564D tert-butyl 4-((4-(1-(6-chloropyridazin-3-yl)azetidine-3-carboxamido)phenyl)sulfonyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 147A, substituting tert-butyl 4-(4-(azetidine-3-carboxamido)phenylsulfonyl)piperidine-1-carboxylate for tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate.

Example 564E tert-butyl 4-((4-(1-(pyridazin-3-yl)azetidine-3-carboxamido)phenyl)sulfonyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 147B, substituting tert-butyl 4-((4-(1-(6-chloropyridazin-3-yl)azetidine-3-carboxamido)phenyl)sulfonyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(6-chloropyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate.

Example 564F N-(4-(piperidin-4-ylsulfonyl)phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting tert-butyl 4-((4-(1-(pyridazin-3-yl)azetidine-3-carboxamido)phenyl)sulfonyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 564G N-(4-{[1-(3-chlorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(4-(piperidin-4-ylsulfonyl)phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 3-chlorobenzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO/D₂O) δ ppm 8.53 (dd, J=4.4, 1.2 Hz, 1H), 7.93-7.84 (m, 2H), 7.84-7.77 (m, 2H), 7.72 (dd, J=9.3, 4.4 Hz, 1H), 7.58-7.38 (m, 2H), 7.40-7.21 (m, 3H), 4.58-4.37 (m, 5H), 4.02 (d, J=31.5 Hz, 3H), 3.88 (tt, J=8.8, 5.9 Hz, 1H), 3.48 (ddd, J=11.6, 7.7, 3.9 Hz, 1H), 2.99 (t, J=11.9 Hz, 2H), 1.92 (d, J=10.6 Hz, 2H), 1.53 (qd, J=12.2, 4.5 Hz, 3H); MS (ESI(+)) m/e 540 (M+H)⁺.

The following Examples were prepared essentially as described in Example 564, substituting the appropriate carboxylic acid in Example 564F. Some products were purified by flash chromatography while others were purified by reverse-phase HPLC. Accordingly, some Examples were isolated as trifluoroacetic acid salts.

TABLE 11 Ex Name MS 565 N-(4-{[1-(4-tert-butylbenzoyl)piperidin-4-yl]sulfonyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 562 (M + H)⁺ 566 N-(4-{[1-(4-methoxybenzoyl)piperidin-4-yl]sulfonyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 536 (M + H)⁺ 567 N-(4-{[1-(4-methylbenzoyl)piperidin-4-yl]sulfonyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 520 (M + H)⁺ 568 N-(4-{[1-(cyclohexylcarbonyl)piperidin-4-yl]sulfonyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 512 (M + H)⁺ 569 N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]sulfonyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 484 (M + H)⁺ 570 N-(4-{[1-(2-methoxybenzoyl)piperidin-4-yl]sulfonyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 536 (M + H)⁺ 571 N-[4-({[1-[(2S)-2-phenylbutanoyl]piperidin-4-yl} (ESI(+)) sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3- m/e 548 carboxamide (M + H)⁺ 572 N-[4-({1-[4-(propan-2-yl)benzoyl]piperidin-4-yl} (ESI(+)) sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3- m/e 548 carboxamide (M + H)⁺ 573 N-(4-{[1-(4-chlorobenzoyl)piperidin-4-yl]sulfonyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 540 (M + H)⁺ 574 N-{4-[(1-benzoylpiperidin-4-yl)sulfonyl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 506 (M + H)⁺ 575 1-(pyridazin-3-yl)-N-(4-{[1-(4,4,4-trifluorobutanoyl) (ESI(+)) piperidin-4-yl]sulfonyl}phenyl)azetidine-3-carboxamide m/e 526 (M + H)⁺ 576 N-(4-{[1-(2,5-difluorobenzoyl)piperidin-4-yl]sulfonyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 542 (M + H)⁺ 577 N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]sulfonyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 524 (M + H)⁺ 578 N-(4-{[1-(2-methylbenzoyl)piperidin-4-yl]sulfonyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 520 (M + H)⁺ 579 N-[4-({1-[(4-fluorophenyl)acetyl]piperidin-4-yl}sulfonyl) (ESI(+)) phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 538 (M + H)⁺ 580 N-(4-{[1-(3-methylbenzoyl)piperidin-4-yl]sulfonyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 520 (M + H)⁺ 581 N-(4-{[1-(2,3-dimethylbenzoyl)piperidin-4-yl]sulfonyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 534 (M + H)⁺ 582 N-[4-({1-[(3-fluorophenyl)acetyl]piperidin-4-yl}sulfonyl) (ESI(+)) phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 538 (M + H)⁺ 583 N-(4-{[1-(3-fluorobenzoyl)piperidin-4-yl]sulfonyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 524 (M + H)⁺ 584 1-(pyridazin-3-yl)-N-[4-({1-[3-(trifluoromethyl)benzoyl] (ESI(+)) piperidin-4-yl}sulfonyl)phenyl]azetidine-3-carboxamide m/e 575 (M + H)⁺ 585 N-[4-({1-[(3,5-difluorophenyl)acetyl]piperidin-4-yl} (ESI(+)) sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3- m/e 556 carboxamide (M + H)⁺ 586 N-(4-{[1-(2,4-difluorobenzoyl)piperidin-4-yl]sulfonyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 542 (M + H)⁺ 587 1-(pyridazin-3-yl)-N-[4-({1-[4-(trifluoromethyl)benzoyl] (ESI(+)) piperidin-4-yl}sulfonyl)phenyl]azetidine-3-carboxamide m/e 574 (M + H)⁺ 588 N-(4-{[1-(4-fluorobenzoyl)piperidin-4-yl]sulfonyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 524 (M + H)⁺ 589 N-(4-{[1-(2,3-difluorobenzoyl)piperidin-4-yl]sulfonyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 542 (M + H)⁺ 590 N-(4-{[1-(2,4-dichlorobenzoyl)piperidin-4-yl]sulfonyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 574 (M + H)⁺ 591 N-(4-{[1-(naphthalen-1-ylcarbonyl)piperidin-4-yl] (ESI(+)) sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3- m/e 556 carboxamide (M + H)⁺ 592 N-(4-{[1-(cyclopropylcarbonyl)piperidin-4-yl]sulfonyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 470 (M + H)⁺ 593 N-(4-{[1-(3,5-difluorobenzoyl)piperidin-4-yl]sulfonyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 542 (M + H)⁺ 594 N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl] (ESI(+)) sulfonyl}phenyl)-1-(pyridazin-3-yl)azetidine-3- m/e 486 carboxamide (M + H)⁺ 595 N-(4-{[1-(3,3-dimethylbutanoyl)piperidin-4-yl]sulfonyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 500 (M + H)⁺ 596 N-(4-{[1-(3-methoxybenzoyl)piperidin-4-yl]sulfonyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 536 (M + H)⁺ 597 N-(4-{[1-(3-methylbutanoyl)piperidin-4-yl]sulfonyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 486 (M + H)⁺ 598 N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]sulfonyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 472 (M + H)⁺ 599 N-(4-{[1-(cyclopentylcarbonyl)piperidin-4-yl]sulfonyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 498 (M + H)⁺ 600 N-(4-{[1-(phenylacetyl)piperidin-4-yl]sulfonyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 520 (M + H)⁺ 601 N-[4-({1-[(1-phenylcyclopropyl)carbonyl]piperidin-4- (ESI(+)) yl}sulfonyl)phenyl]-1-(pyridazin-3-yl)azetidine-3- m/e 546 carboxamide (M + H)⁺ 611 N-(4-{[1-(2-chlorobenzoyl)piperidin-4-yl]sulfonyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 540 (M + H)⁺ 612 N-(4-{[1-(4-methylpentanoyl)piperidin-4-yl]sulfonyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 500 (M + H)⁺ 613 N-[4-({1-[(2-fluorophenyl)acetyl]piperidin-4-yl}sulfonyl) (ESI(+)) phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 538 (M + H)⁺

Example 602 N-{4-[1-(2-methylalanyl)piperidin-4-yl]phenyl}-1-(pyridin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(4-(piperidin-4-yl)phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2-methylalanine for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.14 (s, 1H), 8.18-8.11 (m, 4H), 8.07 (d, J=2.5 Hz, 1H), 7.74 (dd, J=8.6, 5.4 Hz, 1H), 7.55 (d, J=8.5 Hz, 2H), 7.52 (dd, J=8.7, 2.3 Hz, 1H), 7.21 (d, J=8.5 Hz, 2H), 4.41-3.68 (m, 7H), 3.10-2.89 (m, 2H), 2.89-2.74 (m, 1H), 1.85 (d, J=12.3 Hz, 2H), 1.58 (s, 6H), 1.52-1.37 (m, 2H); MS (ESI(+)) m/e 422 (M+H)⁺.

Example 603 5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3R)-1-(pyridin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide Example 603A (R)-tert-butyl 3-(5-(1-isobutyl-1H-pyrazol-4-yl)thiophene-2-carboxamido)pyrrolidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting (R)-tert-butyl 3-aminopyrrolidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 5-(1-isobutyl-1H-pyrazol-4-yl)thiophene-2-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 603B (R)-5-(1-isobutyl-1H-pyrazol-4-yl)-N-(pyrrolidin-3-yl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1D, substituting (R)-tert-butyl 3-(5-(1-isobutyl-1H-pyrazol-4-yl)thiophene-2-carboxamido)pyrrolidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 603C 5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3R)-1-(pyridin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 1C, substituting (R)-5-(1-isobutyl-1H-pyrazol-4-yl)-N-(pyrrolidin-3-yl)thiophene-2-carboxamide for tert-butyl 4-(4-(azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.85 (d, J=6.78 Hz, 6H) 1.90-2.38 (m, 3H) 3.16-3.66 (m, 4H) 3.92 (d, J=7.12 Hz, 2H) 4.59 (d, J=5.76 Hz, 1H) 6.92 (dd, J=8.48, 1.70 Hz, 1H) 7.08-7.27 (m, 2H) 7.72 (d, J=3.73 Hz, 1H) 7.79 (s, 1H) 7.85 (d, J=3.73 Hz, 1H) 7.95 (d, J=2.71 Hz, 1H) 8.13 (s, 1H) 8.54 (d, J=7.12 Hz, 1H); MS (ESI(+)) m/e 396 (M+H)⁺.

Example 604 5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3R)-1-(pyridazin-4-yl)pyrrolidin-3-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 1C, substituting 4-bromopyridazine for 3-bromopyridine and (R)-5-(1-isobutyl-1H-pyrazol-4-yl)-N-(pyrrolidin-3-yl)thiophene-2-carboxamide for tert-butyl 4-(4-(azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.85 (d, J=6.44 Hz, 6H) 1.90-2.39 (m, 3H) 3.38-3.75 (m, 4H) 3.92 (d, J=7.12 Hz, 2H) 4.43-4.71 (m, 1H) 6.62 (dd, J=6.44, 3.05 Hz, 1H) 7.19 (d, J=3.73 Hz, 1H) 7.71 (d, J=4.07 Hz, 1H) 7.79 (s, 1H) 8.13 (s, 1H) 8.55 (dd, J=8.99, 6.95 Hz, 2H) 8.64 (d, J=2.71 Hz, 1H); MS (ESI(+)) m/e 397 (M+H)⁺.

Example 605 5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3R)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide Example 605A (R)—N-(1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl)-5-(1-isobutyl-1H-pyrazol-4-yl)thiophene-2-carboxamide

The title compound was prepared as described in Example 147A, substituting (R)-5-(1-isobutyl-1H-pyrazol-4-yl)-N-(pyrrolidin-3-yl)thiophene-2-carboxamide for tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate.

Example 605B 5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3R)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 1B, substituting (R)—N-(1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl)-5-(1-isobutyl-1H-pyrazol-4-yl)thiophene-2-carboxamide for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 0.85 (d, J=6.71 Hz, 6H) 1.94-2.38 (m, 3H) 3.39-3.84 (m, 4H) 3.92 (d, J=7.32 Hz, 2H) 4.45-4.66 (m, 1H) 6.88 (d, J=8.24 Hz, 1H) 7.19 (d, J=3.97 Hz, 1H) 7.34 (dd, J=9.00, 4.43 Hz, 1H) 7.73 (d, J=3.97 Hz, 1H) 7.80 (s, 1H) 8.14 (s, 1H) 8.49 (d, J=3.66 Hz, 1H) 8.56 (d, J=6.71 Hz, 1H); MS (ESI(+)) m/e 397 (M+H)⁺.

Example 606 5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide Example 606A (S)-tert-butyl 3-(5-(1-isobutyl-1H-pyrazol-4-yl)thiophene-2-carboxamido)pyrrolidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting (S)-tert-butyl 3-aminopyrrolidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 5-(1-isobutyl-1H-pyrazol-4-yl)thiophene-2-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 606B (S)-5-(1-isobutyl-1H-pyrazol-4-yl)-N-(pyrrolidin-3-yl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1D, substituting (S)-tert-butyl 3-(5-(1-isobutyl-1H-pyrazol-4-yl)thiophene-2-carboxamido)pyrrolidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 606C (S)—N-(1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl)-5-(1-isobutyl-1H-pyrazol-4-yl)thiophene-2-carboxamide

The title compound was prepared as described in Example 147A, substituting (S)-5-(1-isobutyl-1H-pyrazol-4-yl)-N-(pyrrolidin-3-yl)thiophene-2-carboxamide for tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate.

Example 606D 5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 1B, substituting (S)—N-(1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl)-5-(1-isobutyl-1H-pyrazol-4-yl)thiophene-2-carboxamide for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.85 (d, J=6.78 Hz, 6H) 1.91-2.42 (m, 3H) 3.49-3.88 (m, 4H) 3.87-4.07 (m, 2H) 4.30-4.81 (m, 1H) 7.20 (d, J=3.73 Hz, 1H) 7.68 (d, J=8.82 Hz, 1H) 7.74-7.94 (m, 3H) 8.14 (s, 1H) 8.58 (d, J=3.05 Hz, 1H) 8.71 (d, J=6.44 Hz, 1H); MS (ESI(+)) m/e 397 (M+H)⁺.

Example 607 5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3S)-1-(pyridazin-4-yl)pyrrolidin-3-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 1C, substituting 4-bromopyridazine for 3-bromopyridine and (S)-5-(1-isobutyl-1H-pyrazol-4-yl)-N-(pyrrolidin-3-yl)thiophene-2-carboxamide for tert-butyl 4-(4-(azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.75-0.98 (m, 6H) 1.98-2.44 (m, 3H) 3.67-4.18 (m, 6H) 4.66 (s, 1H) 7.15 (dd, J=7.12, 3.05 Hz, 1H) 7.21 (d, J=3.73 Hz, 1H) 7.54-7.91 (m, 2H) 8.14 (s, 1H) 8.56-8.95 (m, 3H); MS (ESI(+)) m/e 397 (M+H)⁺.

Example 608 5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3S)-1-(pyridin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 1C, substituting (S)-5-(1-isobutyl-1H-pyrazol-4-yl)-N-(pyrrolidin-3-yl)thiophene-2-carboxamide for tert-butyl 4-(4-(azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.85 (d, J=6.78 Hz, 6H) 1.88-2.38 (m, 3H) 3.11-3.67 (m, 4H) 3.92 (d, J=7.46 Hz, 2H) 4.45-4.76 (m, 1H) 6.75-7.01 (m, 1H) 7.03-7.25 (m, 2H) 7.73 (d, J=4.07 Hz, 1H) 7.79 (s, 1H) 7.81-7.93 (m, 1H) 7.95 (d, J=2.71 Hz, 1H) 8.13 (s, 1H) 8.54 (d, J=7.12 Hz, 1H); MS (ESI(+)) m/e 396 (M+H)⁺.

Example 609 tert-butyl 4-(2-methyl-1-oxo-1-{4-[4-({[1-(pyridin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]piperidin-1-yl}propan-2-yl)piperazine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting N-(4-(piperidin-4-yl)phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2-(4-(tert-butoxycarbonyl)piperazin-1-yl)-2-methylpropanoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ₁H NMR (300 MHz, DMSO-d₆) δ ppm 10.00 (s, 1H), 7.93 (dd, J=4.6, 1.4 Hz, 1H), 7.85 (d, J=2.5 Hz, 1H), 7.53 (d, J=8.6 Hz, 2H), 7.23-7.13 (m, 3H), 6.86 (ddd, J=8.3, 2.9, 1.4 Hz, 1H), 5.43 (bs, 1H), 4.59 (bs, 1H), 4.15-4.03 (m, 2H), 4.02-3.90 (m, 2H), 3.71 (tt, J=8.3, 6.1 Hz, 1H), 3.42-3.32 (m, 4H), 3.04 (bs, 1H), 2.80-2.62 (m, 2H), 2.39 (bs, 4H), 1.78 (d, J=11.1 Hz, 2H), 1.57-1.42 (m, 2H), 1.39 (s, 9H), 1.17 (s, 6H); MS (ESI(+)) m/e 591 (M+H)⁺.

Example 610 N-(4-{1-[2-methyl-2-(piperazin-1-yl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting tert-butyl 4-(2-methyl-1-oxo-1-{4-[4-({[1-(pyridin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]piperidin-1-yl}propan-2-yl)piperazine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.08 (s, 1H), 8.52 (s, 1H), 8.14 (d, J=5.2 Hz, 1H), 8.07 (d, J=2.6 Hz, 1H), 7.76 (dd, J=8.7, 5.4 Hz, 1H), 7.54 (d, J=8.6 Hz, 2H), 7.20 (d, J=8.6 Hz, 2H), 4.88 (bs, 4H), 4.23 (t, J=8.4 Hz, 2H), 4.12 (dd, J=7.9, 5.9 Hz, 2H), 3.87-3.66 (m, 1H), 3.10 (bs, 4H), 2.85-2.54 (m, 5H), 1.79 (d, J=13.1 Hz, 2H), 1.61-1.32 (m, 2H), 1.21 (s, 6H); MS (ESI(+)) m/e 491 (M+H)⁺.

Example 614 N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide Example 614A tert-butyl 4-((4-(1-(5,6-dichloropyridazin-4-yl)azetidine-3 carboxamido)phenyl)sulfonyl)piperidine-1-carboxylate

To 3,4,5-trichloropyridazine (1.624 g, 8.85 mmol) and N-ethyl-N-isopropylpropan-2-amine (2.289 g, 17.71 mmol) in 50 mL N,N-dimethylformamide at 0° C. was added tert-butyl 4-(4-(azetidine-3-carboxamido)phenylsulfonyl)piperidine-1-carboxylate (2.5 g, 5.90 mmol) in ml N,N-dimethylformamide, dropwise. The reaction mixture was stirred from 0° C. to room temperature overnight, diluted with water and extracted with ethyl acetate. The organic layer was dried with magnesium sulfate, filtered, concentrated and purified by flash chromatography to give the title compound.

Example 614B tert-butyl 4-((4-(1-(pyridazin-4-yl)azetidine-3-carboxamido)phenyl)sulfonyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1B, substituting tert-butyl 4-((4-(1-(5,6-dichloropyridazin-4-yl)azetidine-3 carboxamido)phenyl)sulfonyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3 carboxamido)phenoxy)piperidine-1-carboxylate.

Example 614C N-(4-(piperidin-4-ylsulfonyl)phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting tert-butyl 4-((4-(1-(pyridazin-4-yl)azetidine-3-carboxamido)phenyl)sulfonyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 614D N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(4-(piperidin-4-ylsulfonyl)phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and isobutyric acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.70 (s, 1H), 8.79 (d, J=7.2 Hz, 1H), 8.55 (d, J=3.1 Hz, 1H), 7.93-7.86 (m, 2H), 7.85-7.78 (m, 2H), 7.00 (dd, J=7.2, 3.1 Hz, 1H), 4.65-4.36 (m, 5H), 4.09-3.82 (m, 2H), 3.35-2.67 (m, 4H), 1.95-1.76 (m, 2H), 1.48-0.99 (m, 2H), 0.95 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 472 (M+H)⁺.

Example 615 N-{4-[(1-benzoylpiperidin-4-yl)sulfonyl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(4-(piperidin-4-ylsulfonyl)phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and benzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.70 (s, 1H), 8.79 (d, J=7.2 Hz, 1H), 8.55 (d, J=3.3 Hz, 1H), 7.93-7.86 (m, 2H), 7.85-7.78 (m, 2H), 7.49-7.29 (m, 5H), 7.00 (dd, J=7.2, 3.1 Hz, 1H), 4.65-4.35 (m, 4H), 3.99-3.83 (m, 1H), 3.73-3.50 (m, 1H), 3.28-2.65 (m, 4H), 2.37-1.59 (m, 2H), 1.56-1.06 (m, 2H); MS (ESI(+)) m/e 506 (M+H)⁺.

Example 616 N-(4-{[1-(4-fluorobenzoyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(4-(piperidin-4-ylsulfonyl)phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 4-fluorobenzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.70 (s, 1H), 8.79 (d, J=6.9 Hz, 1H), 8.55 (d, J=3.1 Hz, 1H), 7.93-7.86 (m, 2H), 7.85-7.78 (m, 2H), 7.52-7.38 (m, 2H), 7.31-7.20 (m, 2H), 7.00 (dd, J=7.2, 3.1 Hz, 1H), 4.63-4.19 (m, 4H), 3.99-3.83 (m, 1H), 3.73-3.46 (m, 2H), 3.23-2.65 (m, 3H), 2.37-1.60 (m, 2H), 1.56-1.06 (m, 2H); MS (ESI(+)) m/e 524 (M+H)⁺.

Example 617 N-(4-{[1-(cyclopentylcarbonyl)piperidin-4-yl]sulfonyl}phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(4-(piperidin-4-ylsulfonyl)phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and cyclopentanecarboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.69 (s, 1H), 8.79 (d, J=7.2 Hz, 1H), 8.55 (d, J=3.1 Hz, 1H), 7.97-7.77 (m, 4H), 7.00 (dd, J=7.2, 3.1 Hz, 1H), 4.67-4.37 (m, 5H), 4.11-4.01 (m, 1H), 3.99-3.84 (m, 1H), 3.35-2.71 (m, 4H), 1.95-1.06 (m, 10H), 1.07-0.97 (m, 2H); MS (ESI(+)) m/e 498 (M+H)⁺.

Example 618 N-[(3R)-1-(5,6-dichloropyridazin-4-yl)pyrrolidin-3-yl]-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide

3,4,5-Trichloropyridazine (269 mg, 1.464 mmol) was dissolved in 5 ml N,N-dimethylformamide and triethylamine (370 mg, 3.66 mmol) was added. The solution was cooled with an ice-bath when (R)-5-(1-isobutyl-1H-pyrazol-4-yl)-N-(pyrrolidin-3-yl)thiophene-2-carboxamide bistrifluoroacetate (400 mg, 0.732 mmol) in N,N-dimethylformamide was added dropwise. The reaction mixture was stirred from 0° C. to room temperature overnight, diluted with water and extracted with ethyl acetate. The organic layer was dried with magnesium sulfate, filtered, concentrated, and purified by flash chromatography to give the title compound. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 8.66 (s, 1H), 8.49 (d, J=6.5 Hz, 1H), 8.14 (s, 1H), 7.79 (s, 1H), 7.70 (d, J=3.9 Hz, 1H), 7.20 (d, J=3.8 Hz, 1H), 4.59-4.45 (m, 1H), 4.05 (dd, J=11.0, 6.4 Hz, 1H), 4.01-3.66 (m, 5H), 2.30-1.94 (m, 3H), 0.85 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 465 (M+H)⁺.

Example 619 N-[(3R)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 147A, substituting (R)-5-(1-isobutyl-1H-pyrazol-4-yl)-N-(pyrrolidin-3-yl)thiophene-2-carboxamide for tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 8.55 (d, J=6.6 Hz, 1H), 8.14 (s, 1H), 7.80 (s, 1H), 7.72 (d, J=3.9 Hz, 1H), 7.49 (d, J=9.4 Hz, 1H), 7.20 (d, J=3.8 Hz, 1H), 7.03 (d, J=9.4 Hz, 1H), 4.64-4.52 (m, 1H), 3.92 (d, J=7.2 Hz, 2H), 3.76 (dd, J=11.0, 6.6 Hz, 1H), 3.69-3.41 (m, 3H), 2.34-2.21 (m, 1H), 2.19-2.02 (m, 2H), 0.85 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 431 (M+H)⁺.

Example 620 N-[(3S)-1-(5,6-dichloropyridazin-4-yl)pyrrolidin-3-yl]-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 618, substituting (S)-5-(1-isobutyl-1H-pyrazol-4-yl)-N-(pyrrolidin-3-yl)thiophene-2-carboxamide for (R)-5-(1-isobutyl-1H-pyrazol-4-yl)-N-(pyrrolidin-3-yl)thiophene-2-carboxamide. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 8.70 (s, 1H), 8.55 (d, J=6.5 Hz, 1H), 8.19 (s, 1H), 7.85 (s, 1H), 7.75 (d, J=3.9 Hz, 1H), 7.25 (d, J=3.8 Hz, 1H), 4.64-4.47 (m, 1H), 4.10 (dd, J=10.9, 6.4 Hz, 1H), 4.07-3.67 (m, 5H), 2.32-2.02 (m, 3H), 0.94-0.75 (m, 6H); MS (ESI(+)) m/e 465 (M+H)⁺.

Example 621 N-[(3S)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 147A, substituting (S)-5-(1-isobutyl-1H-pyrazol-4-yl)-N-(pyrrolidin-3-yl)thiophene-2-carboxamide for tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 8.54 (d, J=6.7 Hz, 1H), 8.13 (d, J=0.8 Hz, 1H), 7.79 (d, J=0.8 Hz, 1H), 7.72 (d, J=3.9 Hz, 1H), 7.49 (d, J=9.4 Hz, 1H), 7.19 (d, J=3.8 Hz, 1H), 7.03 (d, J=9.4 Hz, 1H), 4.63-4.53 (m, 1H), 3.92 (d, J=7.2 Hz, 2H), 3.76 (dd, J=11.0, 6.6 Hz, 1H), 3.71-3.39 (m, 3H), 2.37-2.00 (m, 3H), 0.85 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 431 (M+H)⁺.

Example 622 N-[(3R)-1-(5,6-dichloropyridazin-4-yl)pyrrolidin-3-yl]-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-3-carboxamide Example 622A 5-(1-isobutyl-1H-pyrazol-4-yl)thiophene-3-carboxylic acid

The title compound was prepared as described as described in Example 148A, substituting 5-bromothiophene-3-carboxylic acid for 4-bromoaniline.

Example 622B (R)-tert-butyl 3-(5-(1-isobutyl-1H-pyrazol-4-yl)thiophene-3-carboxamido)pyrrolidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting (R)-tert-butyl 3-aminopyrrolidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 5-(1-isobutyl-1H-pyrazol-4-yl)thiophene-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 622B (R)-5-(1-isobutyl-1H-pyrazol-4-yl)-N-(pyrrolidin-3-yl)thiophene-3-carboxamide

The title compound was prepared as described in Example 1D, substituting (R)-tert-butyl 3-(5-(1-isobutyl-1H-pyrazol-4-yl)thiophene-3-carboxamido)pyrrolidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 622C N-[(3R)-1-(5,6-dichloropyridazin-4-yl)pyrrolidin-3-yl]-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-3-carboxamide

The title compound was prepared as described in Example 618, substituting (R)-5-(1-isobutyl-1H-pyrazol-4-yl)-N-(pyrrolidin-3-yl)thiophene-3-carboxamide for (R)-5-(1-isobutyl-1H-pyrazol-4-yl)-N-(pyrrolidin-3-yl)thiophene-2-carboxamide. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 8.66 (s, 1H), 8.37 (d, J=6.5 Hz, 1H), 8.08 (d, J=0.8 Hz, 1H), 7.94 (d, J=1.4 Hz, 1H), 7.74 (d, J=0.8 Hz, 1H), 7.51 (d, J=1.4 Hz, 1H), 4.53 (q, J=5.4 Hz, 1H), 4.06 (dd, J=10.9, 6.4 Hz, 1H), 3.98-3.66 (m, 5H), 2.30-1.96 (m, 3H), 0.85 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 465 (M+H)⁺.

Example 623 5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3R)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-3-carboxamide Example 623A (R)—N-(1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl)-5-(1-isobutyl-1H-pyrazol-4-yl)thiophene-3-carboxamide

The title compound was prepared as described in Example 147A, substituting (R)-5-(1-isobutyl-1H-pyrazol-4-yl)-N-(pyrrolidin-3-yl)thiophene-3-carboxamide for tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate.

Example 623B 5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3R)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-3-carboxamide

The title compound was prepared as described in Example 147B, substituting (R)—N-(1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl)-5-(1-isobutyl-1H-pyrazol-4-yl)thiophene-3-carboxamide for 4-(4-(1-(6-chloropyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 8.49 (dd, J=4.5, 1.3 Hz, 1H), 8.41 (d, J=6.7 Hz, 1H), 8.08 (s, 1H), 7.96 (d, J=1.4 Hz, 1H), 7.73 (s, 1H), 7.54 (d, J=1.4 Hz, 1H), 7.37 (dd, J=9.1, 4.4 Hz, 1H), 6.92 (d, J=9.1 Hz, 1H), 4.67-4.55 (m, 1H), 3.92 (d, J=7.2 Hz, 2H), 3.78 (dd, J=10.9, 6.6 Hz, 1H), 3.72-3.41 (m, 3H), 2.40-1.98 (m, 3H), 0.85 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 397 (M+H)⁺.

Example 624 5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3R)-1-(pyridazin-4-yl)pyrrolidin-3-yl]thiophene-3-carboxamide

The title compound was prepared as described in Example 1B, substituting N-[(3R)-1-(5,6-dichloropyridazin-4-yl)pyrrolidin-3-yl]-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-3-carboxamide for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 8.86-8.69 (m, 2H), 8.58 (d, J=6.6 Hz, 1H), 8.08 (d, J=0.8 Hz, 1H), 8.01 (d, J=1.4 Hz, 1H), 7.74 (d, J=0.8 Hz, 1H), 7.55 (d, J=1.4 Hz, 1H), 7.15 (dd, J=7.3, 3.1 Hz, 1H), 4.72-4.59 (m, 1H), 4.08-3.47 (m, 6H), 2.37-1.97 (m, 3H), 0.85 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 397 (M+H)⁺.

Example 625 N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)piperidine-4-carboxamide Example 625A benzyl 4-((4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)carbamoyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting tert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 1-(benzyloxycarbonyl)piperidine-4-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 625B tert-butyl 4-(4-(piperidine-4-carboxamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1B, substituting benzyl 4-((4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)carbamoyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 625C tert-butyl 4-(4-(1-(6-chloropyridazin-3-yl)piperidine-4-carboxamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 147A, substituting tert-butyl 4-(4-(piperidine-4-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate.

Example 625D tert-butyl 4-(4-(1-(pyridazin-3-yl)piperidine-4-carboxamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 147B, tert-butyl 4-(4-(1-(6-chloropyridazin-3-yl)piperidine-4-carboxamido)phenyl)piperidine-1-carboxylate for 4-(4-(1-(6-chloropyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate.

Example 625E N-(4-(piperidin-4-yl)phenyl)-1-(pyridazin-3-yl)piperidine-4-carboxamide

The title compound was prepared as described in Example 1D, substituting tert-butyl 4-(4-(1-(pyridazin-3-yl)piperidine-4-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 625F N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)piperidine-4-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(4-(piperidin-4-yl)phenyl)-1-(pyridazin-3-yl)piperidine-4-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2,2-dimethylpropanoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 9.86 (s, 1H), 8.51 (d, J=3.6 Hz, 1H), 7.53-7.47 (m, 2H), 7.43-7.31 (m, 1H), 7.26 (d, J=8.6 Hz, 1H), 7.17-7.11 (m, 2H), 4.45-4.34 (m, 4H), 2.94 (t, J=11.6 Hz, 1H), 2.82 (t, J=12.5 Hz, 1H), 2.66 (dddd, J=33.0, 15.2, 8.0, 3.6 Hz, 1H), 1.89-1.81 (m, 2H), 1.80-1.71 (m, 2H), 1.70-1.53 (m, 2H), 1.51-1.33 (m, 2H), 1.20 (s, 9H), MS (ESI(+)) m/e 450 (M+H)⁺.

Example 626 N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)piperidine-4-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(4-(piperidin-4-yl)phenyl)-1-(pyridazin-3-yl)piperidine-4-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and benzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 9.87 (s, 1H), 8.51 (d, J=4.8 Hz, 1H), 7.54-7.48 (m, 2H), 7.47-7.36 (m, 5H), 7.35 (dd, J=9.3, 4.4 Hz, 1H), 7.26 (d, J=8.7 Hz, 1H), 7.21-7.15 (m, 2H), 4.60 (s, 1H), 4.46-4.37 (m, 2H), 3.63 (s, 1H), 3.24-2.56 (m, 6H), 1.89-1.80 (m, 2H), 1.80-1.46 (m, 5H), MS (ESI(+)) m/e 470 (M+H)⁺.

Example 627 N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)piperidine-4-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(4-(piperidin-4-yl)phenyl)-1-(pyridazin-3-yl)piperidine-4-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2-fluorobenzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 9.87 (s, 1H), 8.51 (d, J=4.4 Hz, 1H), 7.56-7.38 (m, 4H), 7.35 (dd, J=9.3, 4.4 Hz, 1H), 7.32-7.21 (m, 3H), 7.16 (d, J=8.5 Hz, 2H), 4.64 (d, J=13.1 Hz, 1H), 4.41 (d, J=13.3 Hz, 2H), 3.15 (t, J=12.3 Hz, 1H), 2.93 (dd, J=18.0, 7.3 Hz, 2H), 2.70 (dddd, J=15.1, 11.4, 10.1, 7.0 Hz, 3H), 1.86 (t, J=13.8 Hz, 3H), 1.76-1.39 (m, 5H); MS (ESI(+)) m/e 488 (M+H)⁺.

Example 628 1-(pyridazin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}piperidine-4-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(4-(piperidin-4-yl)phenyl)-1-(pyridazin-3-yl)piperidine-4-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 4,4,4-trifluorobutanoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 9.86 (s, 1H), 8.51 (d, J=4.3 Hz, 1H), 7.49 (t, J=8.9 Hz, 2H), 7.41-7.30 (m, 1H), 7.25 (d, J=9.3 Hz, 1H), 7.14 (d, J=8.5 Hz, 2H), 4.51 (d, J=13.0 Hz, 1H), 4.41 (d, J=13.3 Hz, 2H), 3.94 (d, J=13.4 Hz, 1H), 3.07 (t, J=12.0 Hz, 1H), 2.94 (dd, J=18.1, 7.3 Hz, 2H), 2.77-2.40 (m, 9H), 1.93-1.80 (m, 2H), 1.71 (d, J=25.3 Hz, 2H), 1.58 (dqd, J=29.0, 12.7, 4.0 Hz, 3H), 1.39 (qd, J=12.7, 4.1 Hz, 1H); MS (ESI(+)) m/e 490 (M+H)⁺.

Example 629 N-[(3S)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-3-carboxamide

The title compound was prepared as described in Example 147A, substituting (S)-5-(1-isobutyl-1H-pyrazol-4-yl)-N-(pyrrolidin-3-yl)thiophene-3-carboxamide for tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate. ¹H NMR (500 MHz, DMSO-d₆) δ ppm 8.42 (d, J=6.7 Hz, 1H), 8.08 (s, 1H), 7.96 (d, J=1.3 Hz, 1H), 7.74 (d, J=0.5 Hz, 1H), 7.54 (d, J=1.3 Hz, 1H), 7.49 (d, J=9.5 Hz, 1H), 7.02 (d, J=9.5 Hz, 1H), 4.87-4.44 (m, 1H), 3.92 (d, 2H), 3.94-3.38 (m, 4H), 2.50-1.87 (m, 3H), 0.85 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 431 (M+H)⁺.

Example 664 5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-3-carboxamide

The title compound was prepared as described in Example 147B, substituting N-[(3S)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]thiophene-3-carboxamide for 4-(4-(1-(6-chloropyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 8.58 (dd, J=4.3, 1.2 Hz, 2H), 8.08 (d, J=0.8 Hz, 1H), 8.02 (d, J=1.4 Hz, 1H), 7.86 (dd, J=9.5, 4.3 Hz, 1H), 7.77-7.66 (m, 2H), 7.57 (d, J=1.4 Hz, 1H), 4.70-4.61 (m, 1H), 3.92 (d, J=7.2 Hz, 2H), 3.67-2.93 (m, 4H), 2.41-2.00 (m, 3H), 0.88-0.81 (m, 6H); MS (ESI(+)) m/e 397 (M+H)⁺.

Example 665 N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-fluoro-5-methylpyridin-3-yl)azetidine-3-carboxamide Example 665A benzyl 3((4-(piperidin-4-yl)phenyl)carbamoyl)azetidine-1-carboxylate

The title compound was prepared as described in Example 1D, substituting tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 665B benzyl 3-((4-(1-benzoylpiperidin-4-yl)phenyl)carbamoyl)azetidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting benzyl 3-((4-(piperidin-4-yl)phenyl)carbamoyl)azetidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and benzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 665C N-(4-(1-benzoylpiperidin-4-yl)phenyl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1B, substituting benzyl 3-((4-(1-benzoylpiperidin-4-yl)phenyl) carbamoyl)azetidine-1-carboxylate for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 665D N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-fluoro-5-methylpyridin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1C, substituting 3-bromo-6-fluoro-5-methylpyridine for 3-bromopyridine and N-(4-(1-benzoylpiperidin-4-yl)phenyl)azetidine-3-carboxamide for tert-butyl 4-(4-(azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate. ¹H NMR (400 MHz, DMSO-d₆/D₂O) δ ppm 7.55-7.34 (m, 7H), 7.26-7.14 (m, 3H), 6.98-6.86 (m, 1H), 4.21-4.01 (m, 3H), 3.95 (dd, J=8.8, 4.6 Hz, 2H), 3.69 (ddd, J=8.5, 7.4, 4.3 Hz, 1H), 3.09-2.95 (m, 2H), 2.80 (d, J=0.6 Hz, 1H), 2.23-2.14 (m, 3H), 1.87-1.75 (m, 2H), 1.58 (tt, J=12.8, 6.1 Hz, 2H), 1.11-1.01 (m, 1H); MS (ESI(+)) m/e 473 (M+H)⁺.

The following Examples were essentially prepared as described in Example 665, substituting an appropriate bromoheterocycle in Example 665D.

TABLE 12 Ex Name MS 666 N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(5- (ESI(+)) fluoropyridin-3-yl)azetidine-3-carboxamide m/e 459 (M + H)⁺ 668 N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(2-fluoro-6- (ESI(+)) methylpyridin-3-yl)azetidine-3-carboxamide m/e 473 (M + H)⁺ 737 N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(2- (ESI(+)) cyanopyridin-3-yl)azetidine-3-carboxamide m/e 466 (M + H)⁺ 738 N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(4- (ESI(+)) cyanopyridin-3-yl)azetidine-3-carboxamide m/e 466 (M + H)⁺ 739 N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-fluoro-4- (ESI(+)) methylpyridin-3-yl)azetidine-3-carboxamide m/e 473 (M + H)⁺ 740 N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(5- (ESI(+)) cyanopyridin-3-yl)azetidine-3-carboxamide m/e 466 (M + H)⁺ 741 N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(5- (ESI(+)) methylpyridin-3-yl)azetidine-3-carboxamide m/e 455 (M + H)⁺

Example 667 N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide Example 667A tert-butyl 4-(4-(1-(6-methylpyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1C, substituting 3-bromo-6-methylpyridazine for 3-bromopyridine and tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 667B 1-(6-methylpyridazin-3-yl)-N-(4-(piperidin-4-yl)phenyl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting tert-butyl 4-(4-(1-(6-methylpyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 667C N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting 1-(6-methylpyridazin-3-yl)-N-(4-(piperidin-4-yl)phenyl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and benzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d6) δ 10.02 (s, 1H), 7.54 (d, J=8.5 Hz, 2H), 7.49-7.39 (m, 5H), 7.28 (d, J=9.1 Hz, 1H), 7.22 (d, J=8.5 Hz, 2H), 6.79 (d, J=9.0 Hz, 1H), 4.72-4.51 (m, 1H), 4.19 (t, J=8.2 Hz, 2H), 4.10 (dd, J=7.8, 6.2 Hz, 2H), 3.71 (tt, J=8.5, 6.1 Hz, 2H), 3.21-2.95 (m, 1H), 2.95-2.64 (m, 2H), 2.44 (s, 3H), 1.93-1.46 (m, 4H); (ESI(+)) m/e 456 (M+H)⁺.

The following Examples were essentially prepared as described in Example 667, substituting the appropriate carboxylic acid in Example 667C.

TABLE 13 Ex Name MS 851 N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(6- (ESI(+)) methylpyridazin-3-yl)azetidine-3-carboxamide m/e 474 (M + H)⁺ 852 N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl] (ESI(+)) phenyl}-1-(6-methylpyridazin-3-yl)azetidine-3- m/e 436 carboxamide (M + H)⁺

Example 742 2-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]-1,3-thiazole-5-carboxamide Example 742A 2-(1-isobutyl-1H-pyrazol-4-yl)thiazole-5-carboxylic acid

The title compound was prepared as described in Example 148A, substituting 2-bromothiazole-5-carboxylic acid for 4-bromoaniline.

Example 742B (S)-tert-butyl 3-(2-(1-isobutyl-1H-pyrazol-4-yl)thiazole-5-carboxamido)pyrrolidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting (S)-tert-butyl 3-aminopyrrolidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2-(1-isobutyl-1H-pyrazol-4-yl)thiazole-5-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 742C (S)-2-(1-isobutyl-1H-pyrazol-4-yl)-N-(pyrrolidin-3-yl)thiazole-5-carboxamide

The title compound was prepared as described in Example 1D, substituting (S)-tert-butyl 3-(2-(1-isobutyl-1H-pyrazol-4-yl)thiazole-5-carboxamido)pyrrolidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 742D (S)—N-(1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl)-2-(1-isobutyl-1H-pyrazol-4-yl)thiazole-5-carboxamide

The title compound was prepared as described in Example 147A, substituting (S)-2-(1-isobutyl-1H-pyrazol-4-yl)-N-(pyrrolidin-3-yl)thiazole-5-carboxamide for tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate.

Example 742E 2-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]-1,3-thiazole-5-carboxamide

The title compound was prepared as described in Example 147B, substituting (S)—N-(1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl)-2-(1-isobutyl-1H-pyrazol-4-yl)thiazole-5-carboxamide for 4-(4-(1-(6-chloropyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 8.80 (d, 1H), 8.41 (d, J=0.8 Hz, 1H), 8.30 (s, 1H), 8.28 (s, 1H), 7.90 (s, 1H), 7.34 (dd, J=9.1, 4.5 Hz, 1H), 6.88 (dd, J=9.1, 1.3 Hz, 1H), 4.67-4.52 (m, 1H), 4.03-3.93 (m, 2H), 3.90-3.40 (m, 4H), 2.36-2.02 (m, 3H), 0.89-0.82 (m, 6H); MS (ESI(+)) m/e 398 (M+H)⁺.

Example 743 (3S)—N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(2-methylpyridin-3-yl)pyrrolidine-3-carboxamide Example 743A (S)-tert-butyl 4-(4-(1-((benzyloxy)carbonyl)pyrrolidine-3-carboxamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting tert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and (S)-1-((benzyloxy)carbonyl)pyrrolidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 743B (S)-tert-butyl 4-(4-(pyrrolidine-3-carboxamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1B, substituting (S)-tert-butyl 4-(4-(1-((benzyloxy)carbonyl)pyrrolidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 743C (S)-tert-butyl 4-(4-(1-(2-methylpyridin-3-yl)pyrrolidine-3-carboxamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1C, substituting 3-bromo-2-methylpyridine for 3-bromopyridine and (S)-tert-butyl 4-(4-(pyrrolidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 743D (S)-1-(2-methylpyridin-3-yl)-N-(4-(piperidin-4-yl)phenyl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting (S)-tert-butyl 4-(4-(1-(2-methylpyridin-3-yl)pyrrolidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 743E (3S)—N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(2-methylpyridin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting (S)-1-(2-methylpyridin-3-yl)-N-(4-(piperidin-4-yl)phenyl)pyrrolidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and benzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 9.98 (s, 1H), 7.97 (ddd, J=5.1, 2.2, 1.3 Hz, 2H), 7.69 (dt, J=8.4, 0.9 Hz, 1H), 7.56-7.51 (m, 2H), 7.47-7.41 (m, 5H), 7.24-7.18 (m, 3H), 7.09 (dd, J=8.0, 4.7 Hz, 1H), 4.62 (s, 1H), 3.65 (s, 1H), 3.19 (ddd, J=14.2, 10.1, 6.4 Hz, 4H), 2.76 (t, J=11.9 Hz, 2H), 2.47 (s, 3H), 2.26-2.06 (m, 2H), 1.93-1.49 (m, 4H), 1.23 (s, 1H), MS (ESI(+)) m/e 469.3 (M+H)⁺.

Example 744 (3S)—N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(2-methylpyridin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting (S)-1-(2-methylpyridin-3-yl)-N-(4-(piperidin-4-yl)phenyl)pyrrolidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2-fluorobenzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 9.98 (s, 1H), 8.01-7.93 (m, 2H), 7.58-7.45 (m, 2H), 7.44-7.37 (m, 1H), 7.30 (tdd, J=6.6, 3.7, 2.8 Hz, 2H), 7.20 (dd, J=11.4, 4.7 Hz, 2H), 7.09 (dd, J=8.1, 4.6 Hz, 1H), 4.66 (d, J=13.1 Hz, 1H), 3.49-3.14 (m, 8H), 2.90-2.69 (m, 2H), 2.47 (s, 3H), 2.31-2.06 (m, 2H), 1.92-1.80 (m, 1H), 1.70 (s, 1H), 1.64-1.41 (m, 2H); MS (ESI(+)) m/e 487.3 (M+H)⁺.

Example 745 (3S)-1-(2-methylpyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting (S)-1-(2-methylpyridin-3-yl)-N-(4-(piperidin-4-yl)phenyl)pyrrolidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 4,4,4-trifluorobutanoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 9.97 (s, 1H), 7.97 (dd, J=4.8, 3.6 Hz, 2H), 7.53 (d, J=8.3 Hz, 3H), 7.24-7.13 (m, 3H), 4.53 (d, J=12.9 Hz, 1H), 3.97 (d, J=13.3 Hz, 1H), 3.39 (d, J=7.5 Hz, 3H), 3.36-3.29 (m, 2H), 3.25-3.16 (m, 2H), 3.11 (dd, J=24.4, 11.8 Hz, 1H), 2.70 (ddd, J=15.1, 11.8, 8.3 Hz, 1H), 2.67-2.57 (m, 3H), 2.47 (s, 3H), 2.27-2.07 (m, 2H), 1.75 (s, 2H), 1.56 (dt, J=12.5, 8.7 Hz, 1H), 1.41 (qd, J=12.8, 4.3 Hz, 1H), MS (ESI(+)) m/e 489.3 (M+H)⁺.

Example 746 N-[(3S)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]furan-2-carboxamide Example 746A 5-(1-isobutyl-1H-pyrazol-4-yl)furan-2-carboxylic acid

The title compound was prepared as described in Example 148A, substituting 5-bromofuran-2-carboxylic acid for 4-bromoaniline.

Example 746B (S)-tert-butyl 3-(5-(1-isobutyl-1H-pyrazol-4-yl)furan-2-carboxamido)pyrrolidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting (S)-tert-butyl 3-aminopyrrolidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 5-(1-isobutyl-1H-pyrazol-4-yl)furan-2-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 746C (S)-5-(1-isobutyl-1H-pyrazol-4-yl)-N-(pyrrolidin-3-yl)furan-2-carboxamide

The title compound was prepared as described in Example 1D, substituting (S)-tert-butyl 3-(5-(1-isobutyl-1H-pyrazol-4-yl)furan-2-carboxamido)pyrrolidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 746D N-[(3S)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]furan-2-carboxamide

The title compound was prepared as described in Example 147A, substituting (S)-5-(1-isobutyl-1H-pyrazol-4-yl)-N-(pyrrolidin-3-yl)furan-2-carboxamide for tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 8.37 (d, J=6.9 Hz, 1H), 8.14 (s, 1H), 7.87 (s, 1H), 7.49 (d, J=9.4 Hz, 1H), 7.17 (d, J=3.5 Hz, 1H), 7.03 (d, J=9.4 Hz, 1H), 6.63 (d, J=3.5 Hz, 1H), 4.69-4.54 (m, 1H), 3.95 (d, J=7.2 Hz, 2H), 3.79 (dd, J=11.0, 6.8 Hz, 1H), 3.72-3.58 (m, 1H), 3.60-3.39 (m, 2H), 2.36-2.19 (m, 1H), 2.22-2.03 (m, 2H), 0.85 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 415 (M+H)⁺.

Example 747 5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]furan-2-carboxamide

The title compound was prepared as described in Example 147B, substituting N-[(3S)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]-5-[1-(2-methylpropyl)-1H-pyrazol-4-yl]furan-2-carboxamide for 4-(4-(1-(6-chloropyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 8.49 (dd, J=4.5, 1.2 Hz, 1H), 8.38 (d, J=7.0 Hz, 1H), 8.15 (s, 1H), 7.87 (s, 1H), 7.34 (dd, J=9.1, 4.4 Hz, 1H), 7.17 (d, J=3.5 Hz, 1H), 6.88 (dd, J=9.1, 1.3 Hz, 1H), 6.63 (d, J=3.5 Hz, 1H), 4.70-4.54 (m, 1H), 3.95 (d, J=7.2 Hz, 2H), 3.79 (dd, J=10.8, 6.9 Hz, 1H), 3.75-3.61 (m, 1H), 3.61-3.39 (m, 2H), 2.37-2.01 (m, 3H), 0.85 (d, J=6.7 Hz, 6H); MS (ESI(+)) m/e 381 (M+H)⁺.

Example 748 N-(4-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide Example 748A 1-(6-chloropyridazin-3-yl)azetidine-3-carboxylic acid

The title compound was prepared as described in Example 147A, substituting azetidine-3-carboxylic acid for tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate.

Example 748B 1-(pyridazin-3-yl)azetidine-3-carboxylic acid

The title compound was prepared as described in Example 147B, substituting 1-(6-chloropyridazin-3-yl)azetidine-3-carboxylic acid for 4-(4-(1-(6-chloropyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate.

Example 748C N-(4-bromophenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting 4-bromoaniline for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 1-(pyridazin-3-yl)azetidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 748D N-(4-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 148A, substituting 1-((4-methyltetrahydro-2H-pyran-4-yl)methyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and N-(4-bromophenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for 4-bromoaniline. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.09 (s, 1H), 8.56 (dd, J=4.5, 1.2 Hz, 1H), 8.06 (s, 1H), 7.82 (s, 1H), 7.61 (d, J=8.7 Hz, 2H), 7.52 (d, J=8.6 Hz, 2H), 7.38 (dd, J=9.0, 4.5 Hz, 1H), 6.83 (dd, J=9.0, 1.2 Hz, 1H), 4.25 (t, J=8.3 Hz, 2H), 4.16 (dd, J=8.0, 6.0 Hz, 2H), 4.02 (s, 2H), 3.84-3.62 (m, 3H), 3.52 (ddd, J=11.8, 9.2, 3.0 Hz, 2H), 1.51 (ddd, J=13.3, 9.0, 4.2 Hz, 2H), 1.32-1.17 (m, 2H), 0.97 (s, 3H); MS (ESI(+)) m/e 433 (M+H)⁺.

Example 749 N-[(3S)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]-4-[1-(2-methylpropanoyl)piperidin-4-yl]benzamide Example 749A (S)-tert-butyl (1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl)carbamate

The title compound was prepared as described in Example 147A, substituting (S)-tert-butyl pyrrolidin-3-ylcarbamate for tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate.

Example 749B (S)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-amine

The title compound was prepared as described in Example 1D, substituting (S)-tert-butyl (1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl)carbamate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 749C N-[(3S)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]-4-[1-(2-methylpropanoyl)piperidin-4-yl]benzamide

The title compound was prepared as described in Example 1A, substituting (S)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-amine for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 4-(1-isobutyrylpiperidin-4-yl)benzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 8.53 (d, J=6.6 Hz, 1H), 7.83-7.76 (m, 2H), 7.48 (d, J=9.4 Hz, 1H), 7.37-7.30 (m, 2H), 7.01 (d, J=9.5 Hz, 1H), 4.68-4.49 (m, 2H), 4.12-4.00 (m, 1H), 3.77 (dd, J=11.0, 6.6 Hz, 1H), 3.68-3.39 (m, 3H), 3.19-3.00 (m, 1H), 3.02-2.50 (m, 3H), 2.35-2.19 (m, 1H), 2.08 (dq, J=12.5, 6.3 Hz, 1H), 1.91-1.70 (m, 2H), 1.65-1.07 (m, 2H). 1.05-0.88 (m, 6H); MS (ESI(+)) m/e 456 (M+H)⁺.

Example 750 N-(4-{1-[2-(piperazin-1-yl)ethyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide Example 750A tert-butyl 4-(2-(4-(4-(1-(pyridazin-3-yl)azetidine-3-carboxamido)phenyl)-1H-pyrazol-1-yl)ethyl)piperazine-1-carboxylate

The title compound was prepared as described in Example 148A, substituting tert-butyl 4-(2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)ethyl)piperazine-1-carboxylate for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and N-(4-bromophenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for 4-bromoaniline.

Example 750B N-(4-{1-[2-(piperazin-1-yl)ethyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting tert-butyl 4-(2-(4-(4-(1-(pyridazin-3-yl)azetidine-3-carboxamido)phenyl)-1H-pyrazol-1-yl)ethyl)piperazine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.20 (s, 1H), 8.71 (s, 2H), 8.57 (dd, J=4.3, 1.0 Hz, 1H), 8.14 (s, 1H), 7.86 (s, 1H), 7.80 (dd, J=9.4, 4.4 Hz, 1H), 7.66-7.58 (m, 2H), 7.57-7.49 (m, 2H), 7.45 (d, J=9.2 Hz, 1H), 4.56-4.36 (m, 4H), 4.31 (t, J=6.3 Hz, 2H), 3.91-3.73 (m, 1H), 3.25-3.09 (m, 4H), 3.04 (t, J=6.1 Hz, 2H), 2.83 (s, 4H); MS (ESI(+)) m/e 433 (M+H)⁺.

Example 751 N-{4-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 148A, substituting 1-neopentyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and N-(4-bromophenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for 4-bromoaniline. ¹H NMR (500 MHz, DMSO-d₆) δ ppm 10.14 (s, 1H), 8.57 (dd, J=4.5, 1.2 Hz, 1H), 8.05 (s, 1H), 7.82 (s, 1H), 7.66-7.58 (m, 2H), 7.55-7.51 (m, 2H), 7.48 (dd, J=9.1, 4.5 Hz, 1H), 6.98 (dd, J=9.1, 1.1 Hz, 1H), 4.30 (t, J=8.6 Hz, 2H), 4.22 (dd, J=8.4, 6.0 Hz, 2H), 3.90 (s, 2H), 3.77 (tt, J=8.6, 5.9 Hz, 1H), 0.92 (s, 9H); MS (ESI(+)) m/e 391 (M+H)⁺.

Example 752 4-[1-(2-methylpropanoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]benzamide

The title compound was prepared as described in Example 147B, substituting N-[(3S)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]-4-[1-(2-methylpropanoyl)piperidin-4-yl]benzamide for 4-(4-(1-(6-chloropyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 8.69 (d, J=6.6 Hz, 1H), 8.57 (dd, J=4.3, 1.2 Hz, 1H), 8.16-7.75 (m, 3H), 7.69 (dd, J=9.5, 1.2 Hz, 1H), 7.37-7.31 (m, 2H), 4.90-4.41 (m, 2H), 4.33-3.60 (m, 5H), 3.20-2.50 (m, 4H), 2.37-2.14 (m, 2H), 1.87-1.74 (m, 2H), 1.63-1.20 (m, 2H), 1.02 (bs, J=7.4 Hz, 6H); MS (ESI(+)) m/e 422 (M+H)⁺.

Example 753 N-{4-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 148A, substituting 2-methyl-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propan-2-ol for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and N-(4-bromophenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for 4-bromoaniline. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.09 (s, 1H), 8.56 (dd, J=4.5, 1.3 Hz, 1H), 8.01 (s, 1H), 7.81 (s, 1H), 7.69-7.57 (m, 2H), 7.57-7.44 (m, 2H), 7.38 (dd, J=9.0, 4.5 Hz, 1H), 6.83 (dd, J=9.0, 1.3 Hz, 1H), 4.70 (s, 1H), 4.25 (t, J=8.4 Hz, 2H), 4.16 (dd, J=8.0, 6.0 Hz, 2H), 4.01 (s, 2H), 3.74 (tt, J=8.5, 6.0 Hz, 1H), 1.08 (s, 6H); MS (ESI(+)) m/e 393 (M+H)⁺.

Example 754 5-[1-(3-fluorobenzoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide Example 754A (S)-tert-butyl (1-(pyridazin-3-yl)pyrrolidin-3-yl)carbamate

The title compound was prepared as described in Example 147B, substituting (S)-tert-butyl (1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl)carbamate for 4-(4-(1-(6-chloropyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate.

Example 754B (S)-1-(pyridazin-3-yl)pyrrolidin-3-amine

The title compound was prepared as described in Example 1D, substituting (S)-tert-butyl (1-(pyridazin-3-yl)pyrrolidin-3-yl)carbamate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 754C 5-(1-(tert-butoxycarbonyl)-1,2,3,6-tetrahydropyridin-4-yl)thiophene-2-carboxylic acid

The title compound was prepared as described in Example 148A, substituting tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 5-bromothiophene-2-carboxylic acid for 4-bromoaniline.

Example 754D 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)thiophene-2-carboxylic acid

The title compound was prepared as described in Example 1B, substituting 5-(1-(tert-butoxycarbonyl)-1,2,3,6-tetrahydropyridin-4-yl)thiophene-2-carboxylic acid for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 754E (S)-tert-butyl 4-(5-((1-(pyridazin-3-yl)pyrrolidin-3-yl)carbamoyl)thiophen-2-yl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting (S)-1-(pyridazin-3-yl)pyrrolidin-3-amine for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)thiophene-2-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 754F (S)-5-(piperidin-4-yl)-N-(1-(pyridazin-3-yl)pyrrolidin-3-yl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1D, substituting (S)-tert-butyl 4-(5-((1-(pyridazin-3-yl)pyrrolidin-3-yl)carbamoyl)thiophen-2-yl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 754G 5-[1-(3-fluorobenzoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting (S)-5-(piperidin-4-yl)-N-(1-(pyridazin-3-yl)pyrrolidin-3-yl)thiophene-2-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 3-fluorobenzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 8.63-8.44 (m, 2H), 7.66 (d, J=3.8 Hz, 1H), 7.58-7.44 (m, 1H), 7.41-7.19 (m, 4H), 6.95 (d, J=3.8 Hz, 1H), 6.87 (dd, J=9.1, 1.4 Hz, 1H), 4.66-4.19 (m, 2H), 3.85-3.38 (m, 5H), 3.20-2.72 (m, 3H), 2.34-2.15 (m, 1H), 2.17-1.78 (m, 3H), 1.72-1.46 (m, 2H); MS (ESI(+)) m/e 480 (M+H)⁺.

The following Examples were essentially prepared as described in Example 754, substituting an appropriate carboxylic acid in Example 754G.

TABLE 14 Ex Name MS 755 5-[1-(4-fluorobenzoyl)piperidin-4-yl]-N-[(3S)-1- (ESI(+)) (pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide m/e 480 (M + H)⁺ 758 N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]-5-[1- (ESI(+)) (tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl] m/e 470 thiophene-2-carboxamide (M + H)⁺ 760 5-[1-(2-methylpropanoyl)piperidin-4-yl]-N-[(3S)-1- (ESI(+)) (pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide m/e 428 (M + H)⁺ 761 5-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-N-[(3S)-1- (ESI(+)) (pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide m/e 498 (M + H)⁺ 762 5-{1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}-N- (ESI(+)) [(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2- m/e 440 carboxamide (M + H)⁺ 763 5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-[(3S)-1- (ESI(+)) (pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide m/e 480 (M + H)⁺ 764 5-(1-benzoylpiperidin-4-yl)-N-[(3S)-1-(pyridazin-3-yl) (ESI(+)) pyrrolidin-3-yl]thiophene-2-carboxamide m/e 462 (M + H)⁺ 765 N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]-5-[1- (ESI(+)) (tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]thiophene- m/e 456 2-carboxamide (M + H)⁺ 766 N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]-5-{1-[(2R)- (ESI(+)) tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}thiophene-2- m/e 456 carboxamide (M + H)⁺ 767 5-{1-[(1-methylpiperidin-4-yl)acetyl]piperidin-4-yl}-N- (ESI(+)) [(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene- m/e 498 2-carboxamide (M + H)⁺ 768 N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]-5-[1-(1,3- (ESI(+)) thiazol-4-ylcarbonyl)piperidin-4-yl]thiophene-2- m/e 469 carboxamide (M + H)⁺ 1013 5-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-N-[(3S)-1- (ESI(+)) (pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide m/e 442 (M + H)⁺ 1014 5-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-N-[(3S)-1- (ESI(+)) (pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide m/e 456 (M + H)⁺ 1015 5-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]-N-[(3S)-1- (ESI(+)) (pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2-carboxamide m/e 456 (M + H)⁺ 1016 5-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}-N- (ESI(+)) [(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene- m/e 440 2-carboxamide (M + H)⁺ 1017 N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl-5-[1-(3,3,3- (ESI(+)) trifluoropropanoyl)piperidin-4-yl]thiophene-2- m/e 468 carboxamide (M + H)⁺ 1018 5-[1-(cyclopropylacetyl)piperidin-4-yl]-N-[(3S)-1- (ESI(+)) (pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2- m/e 440 carboxamide (M + H)⁺ 1019 5-[1-(bicyclo[2.2.1]hept-2-ylacetyl)piperidin-4-yl]-N- (ESI(+)) [(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]thiophene-2- m/e 494 carboxamide (M + H)⁺

Example 756 (3S)—N-(4-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide Example 756A (S)-1-(6-chloropyridazin-3-yl)pyrrolidine-3-carboxylic acid

The title compound was prepared as described in Example 147A, substituting (S)-pyrrolidine-3-carboxylic acid for tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate.

Example 756B (S)-1-(pyridazin-3-yl)pyrrolidine-3-carboxylic acid

The title compound was prepared as described in Example 147B, substituting (S)-1-(6-chloropyridazin-3-yl)pyrrolidine-3-carboxylic acid for 4-(4-(1-(6-chloropyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate.

Example 756C (S)—N-(4-bromophenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting 4-bromoaniline for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and (S)-1-(pyridazin-3-yl)pyrrolidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 756D (3S)—N-(4-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 148A, substituting 1-((4-methyltetrahydro-2H-pyran-4-yl)methyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and (S)—N-(4-bromophenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide for 4-bromoaniline. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.11 (s, 1H), 8.48 (dd, J=4.5, 1.2 Hz, 1H), 8.07 (s, 1H), 7.82 (s, 1H), 7.64-7.58 (m, 2H), 7.54-7.49 (m, 2H), 7.34 (dd, J=9.1, 4.4 Hz, 1H), 6.88 (dd, J=9.2, 1.3 Hz, 1H), 4.02 (s, 2H), 3.78 (dd, J=10.5, 7.9 Hz, 1H), 3.72-3.58 (m, 4H), 3.56-3.45 (m, 3H), 3.37-3.32 (m, 1H), 2.42-2.09 (m, 2H), 1.51 (ddd, J=13.4, 9.1, 4.2 Hz, 2H), 1.32-1.12 (m, 2H), 0.97 (s, 3H); MS (ESI(+)) m/e 447 (M+H)⁺.

The following Examples were essentially prepared as described in Example 756, substituting an appropriate boronate in Example 756D.

TABLE 15 Ex Name MS 757 (3S)-N-{4-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4- (ESI(+)) yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 407 (M + H)⁺ 759 (3S)-N-{4-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl] (ESI(+)) phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 405 (M + H)⁺ 769 (3S)-N-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl] (ESI(+)) phenyl}-1-(pyridazin-3-yl)pyrrolidine-3- m/e 391 carboxamide (M + H)⁺ 770 (3S)-N-{4-[1-(propan-2-yl)-1H-pyrazol-4-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 377 (M + H)⁺ 771 (3S)-N-{4-[1-(cyclopropylmethyl)-1H-pyrazol-4-yl] (ESI(+)) phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 389 (M + H)⁺ 772 (3S)-1-(pyridazin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-2- (ESI(+)) ylmethyl)-1H-pyrazol-4-yl]phenyl}pyrrolidine-3- m/e 433 carboxamide (M + H)⁺ 773 (3S)-N-[4-(1-tert-butyl-1H-pyrazol-4-yl)phenyl]-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 391 (M + H)⁺

Example 774 (3S)—N-(4-{[(3R)-1-benzoylpyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide Example 774A (R)-tert-butyl 3-(4-((S)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamido)phenoxy)pyrrolidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting (R)-tert-butyl 3-(4-aminophenoxyl)pyrrolidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and (S)-1-(pyridazin-3-yl)pyrrolidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 774B (S)-1-(pyridazin-3-yl)-N-(4-((R)-pyrrolidin-3-yloxy)phenyl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting (R)-tert-butyl 3-(4-((S)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamido)phenoxy)pyrrolidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 774C (3S)—N-(4-{[(3R)-1-benzoylpyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting (S)-1-(pyridazin-3-yl)-N-(4-((R)-pyrrolidin-3-yloxy)phenyl)pyrrolidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and benzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.03 (d, J=18.3 Hz, 1H), 8.51 (d, J=4.2 Hz, 1H), 7.46 (tdt, J=21.9, 19.2, 10.8 Hz, 8H), 7.13-7.02 (m, 1H), 6.96 (d, J=8.9 Hz, 1H), 6.86 (d, J=8.9 Hz, 1H), 5.00 (d, J=34.1 Hz, 1H), 3.88-3.74 (m, 2H), 3.65 (dd, J=12.1, 7.4 Hz, 4H), 3.51 (d, J=7.3 Hz, 2H), 2.37-1.98 (m, 4H), MS (ESI(+)) m/e 458 (M+H)⁺.

The following Examples were essentially prepared as described in Example 774, substituting an appropriate carboxylic acid in Example 774C.

TABLE 16 Ex Name MS 775 (3S)-N-(4-{[(3R)-1-(2-fluorobenzoyl)pyrrolidin-3-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 476 (M + H)⁺ 776 (3S)-N-(4-{[(3R)-1-(3-fluorobenzoyl)pyrrolidin-3-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 476 (M + H)⁺ 777 (3S)-N-(4-{[(3R)-1-(4-fluorobenzoyl)pyrrolidin-3-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 476 (M + H)⁺ 778 (3S)-N-(4-{[(3R)-1-(3,5-difluorobenzoyl)pyrrolidin-3- (ESI(+)) yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3- m/e 494 carboxamide (M + H)⁺ 779 (3S)-N-(4-{[(3R)-1-(2-methylbenzoyl)pyrrolidin-3-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 472 (M + H)⁺ 780 (3S)-N-(4-{[(3R)-1-(2,2-dimethylpropanoyl)pyrrolidin-3- (ESI(+)) yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3- m/e 438 carboxamide (M + H)⁺ 781 (3S)-N-[4-({(3R)-1-[(4,4-difluorocyclohexyl)carbonyl] (ESI(+)) pyrrolidin-3-yl}oxy)phenyl]-1-(pyridazin-3-yl)pyrrolidine- m/e 500 3-carboxamide (M + H)⁺ 782 (3S)-1-(pyridazin-3-yl)-N-(4-{[(3R)-1-(4,4,4- (ESI(+)) trifluorobutanoyl)pyrrolidin-3-yl]oxy}phenyl)pyrrolidine- m/e 478 3-carboxamide (M + H)⁺ 783 (3S)-N-(4-{[(3R)-1-(2,4-difluorobenzoyl)pyrrolidin-3- (ESI(+)) yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3- m/e 494 carboxamide (M + H)⁺

Example 784 N-[4-(5-propyl-1,2,4-oxadiazol-3-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 806, substituting butanoyl chloride for 3,3-dimethylbutanoyl chloride in Example 806A. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.39 (s, 1H), 8.57 (dd, J=4.5, 1.3 Hz, 1H), 8.04-7.89 (m, 2H), 7.89-7.74 (m, 2H), 7.38 (dd, J=9.0, 4.5 Hz, 1H), 6.84 (dd, J=8.9, 1.4 Hz, 1H), 4.26 (t, J=8.4 Hz, 2H), 4.18 (dd, J=8.2, 5.9 Hz, 2H), 3.79 (tt, J=8.6, 5.9 Hz, 1H), 2.96 (t, J=7.4 Hz, 2H), 1.81 (h, J=7.4 Hz, 2H), 0.99 (t, J=7.4 Hz, 3H); MS (ESI(+)) m/e 365 (M+H)⁺.

Example 785 (3S)—N-{4-[1-(2-fluorobenzoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide Example 785A (S)-tert-butyl 3-(4-(1-(pyridazin-3-yl)pyrrolidine-3-carboxamido)phenyl)azetidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting tert-butyl 3-(4-aminophenyl)azetidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and substituting (S)-1-(pyridazin-3-yl)pyrrolidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 785B (S)—N-(4-(azetidin-3-yl)phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting (S)-tert-butyl 3-(4-(1-(pyridazin-3-yl)pyrrolidine-3-carboxamido)phenyl)azetidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 785C (3S)—N-{4-[1-(2-fluorobenzoyl)azetidin-3-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting (S)—N-(4-(azetidin-3-yl)phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2-fluorobenzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (500 MHz, DMSO-d₆) δ ppm 10.15 (bs, 1H), 8.51-8.46 (m, 1H), 7.67-7.40 (m, 4H), 7.40-7.24 (m, 5H), 6.90-6.85 (m, 1H), 4.50-4.42 (m, 1H), 4.41-4.34 (m, 1H), 4.02-3.96 (m, 2H), 3.93-3.83 (m, 1H), 3.81-3.73 (m, 1H), 3.67-3.58 (m, 2H), 3.53-3.44 (m, 1H), 3.40-3.30 (m, 1H), 2.43-2.12 (m, 2H); MS (ESI(+)) m/e 446 (M+H)⁺.

The following Examples were essentially prepared as described in Example 785, substituting an appropriate carboxylic acid in Example 785C.

TABLE 17 Ex Name MS 786 (3S)-N-{4-[1-(3-fluorobenzoyl)azetidin-3-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 446 (M + H)⁺ 787 (3S)-N-{4-[1-(4-fluorobenzoyl)azetidin-3-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 446 (M + H)⁺ 788 (3S)-N-[4-(1-benzoylazetidin-3-yl)phenyl]-1-(pyridazin-3- (ESI(+)) yl)pyrrolidine-3-carboxamide m/e 428 (M + H)⁺ 789 (3S)-N-{4-[1-(2,2-dimethylpropanoyl)azetidin-3-yl] (ESI(+)) phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 408 (M + H)⁺ 790 (3S)-N-{4-[1-(3,5-difluorobenzoyl)azetidin-3-yl] (ESI(+)) phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 464 (M + H)⁺ 791 3S)-N-{4-[1-(2-methylbenzoyl)azetidin-3-yl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 442 (M + H)⁺ 792 (3S)-N-{4-[1-(2,4-difluorobenzoyl)azetidin-3-yl] (ESI(+)) phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 464 (M + H)⁺

Example 793 (3R)—N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide Example 793A (R)-1-(6-chloropyridazin-3-yl)pyrrolidine-3-carboxylic acid

The title compound was prepared as described in Example 147A, substituting (R)-pyrrolidine-3-carboxylic acid for tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate.

Example 793B (R)-1-(pyridazin-3-yl)pyrrolidine-3-carboxylic acid

The title compound was prepared as described in Example 147B, substituting (R)-1-(6-chloropyridazin-3-yl)pyrrolidine-3-carboxylic acid for 4-(4-(1-(6-chloropyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate.

Example 793C (R)-tert-butyl 4-(4-(1-(pyridazin-3-yl)pyrrolidine-3-carboxamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting tert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and (R)-1-(pyridazin-3-yl)pyrrolidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 793D (R)—N-(4-(piperidin-4-yl)phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting (R)-tert-butyl 4-(4-(1-(pyridazin-3-yl)pyrrolidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 793E (3R)—N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting (R)—N-(4-(piperidin-4-yl)phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and benzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.06 (s, 1H), 8.48 (dd, J=4.4, 0.9 Hz, 1H), 7.54 (t, J=6.3 Hz, 2H), 7.47-7.40 (m, 5H), 7.35 (dd, J=9.1, 4.5 Hz, 1H), 7.22 (d, J=8.6 Hz, 2H), 6.89 (dd, J=9.2, 1.1 Hz, 1H), 4.62 (s, 1H), 3.75 (dt, J=25.9, 12.9 Hz, 1H), 3.62 (td, J=10.2, 5.8 Hz, 3H), 3.55-3.41 (m, 1H), 3.13 (s, 1H), 2.98-2.69 (m, 2H), 2.39-2.11 (m, 2H), 1.90-1.48 (m, 4H), MS (ESI(+)) m/e 456 (M+H)⁺.

Example 794 (3R)—N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting (R)—N-(4-(piperidin-4-yl)phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2-fluorobenzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.06 (s, 1H), 8.48 (dd, J=4.5, 1.2 Hz, 1H), 7.59-7.40 (m, 4H), 7.41-7.23 (m, 3H), 7.19 (d, J=8.5 Hz, 2H), 6.89 (dd, J=9.2, 1.2 Hz, 1H), 4.66 (d, J=13.1 Hz, 1H), 3.77 (dd, J=10.5, 7.9 Hz, 1H), 3.73-3.56 (m, 2H), 3.48 (dt, J=10.2, 7.4 Hz, 2H), 3.17 (t, J=12.1 Hz, 1H), 2.82 (dt, J=24.1, 11.3 Hz, 2H), 2.38-2.09 (m, 2H), 1.97-1.79 (m, 1H), 1.69 (t, J=17.4 Hz, 1H), 1.52 (ddd, J=20.9, 12.0, 6.1 Hz, 2H), MS (ESI(+)) m/e 474 (M+H)⁺.

Example 795 (3R)—N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting (R)—N-(4-(piperidin-4-yl)phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2,2-dimethylpropanoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.04 (s, 1H), 8.48 (dd, J=4.5, 1.3 Hz, 1H), 7.54 (t, J=6.4 Hz, 1H), 7.34 (dd, J=9.1, 4.5 Hz, 1H), 7.21-7.14 (m, 2H), 6.87 (dd, J=9.1, 1.3 Hz, 1H), 4.46-4.35 (m, 2H), 3.76 (dd, J=10.5, 7.9 Hz, 1H), 3.69-3.54 (m, 2H), 3.48 (dt, J=10.2, 7.4 Hz, 1H), 2.94-2.63 (m, 3H), 2.39-2.07 (m, 2H), 1.83-1.73 (m, 2H), 1.50 (s, 1H), 1.22 (s, 9H), MS (ESI(+)) m/e 436 (M+H)⁺.

Example 796 (3S)—N-(4-{[1-(cyclohexylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide Example 796A (S)-tert-butyl 4-(4-(1-(pyridazin-3-yl)pyrrolidine-3-carboxamido)phenoxy)piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and (S)-1-(pyridazin-3-yl)pyrrolidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 796B (S)—N-(4-(piperidin-4-yloxy)phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting (S)-tert-butyl 4-(4-(1-(pyridazin-3-yl)pyrrolidine-3-carboxamido)phenoxy)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 796C (3S)—N-(4-{[1-(cyclohexylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting (S)—N-(4-(piperidin-4-yloxy)phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and cyclohexanecarboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 9.97 (s, 1H), 8.48 (dd, J=4.5, 1.3 Hz, 1H), 7.55-7.48 (m, 2H), 7.34 (dd, J=9.1, 4.4 Hz, 1H), 6.97-6.84 (m, 3H), 4.58-4.47 (m, 1H), 3.88-3.40 (m, 6H), 3.40-3.20 (m, 2H), 2.60-2.50 (m, 1H), 2.41-2.08 (m, 2H), 2.00-1.80 (m, 2H), 1.77-1.07 (m, 13H); MS (ESI(+)) m/e 478 (M+H)⁺.

The following Examples were essentially prepared as described in Example 796, substituting an appropriate carboxylic acid in Example 796C.

TABLE 18 Ex Name MS 797 (3S)-N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 490 (M + H)⁺ 798 (3S)-N-(4-{[1-(3-fluorobenzoyl)piperidin-4-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 490 (M + H)⁺ 799 (3S)-N-{4-[(1-benzoylpiperidin-4-yl)oxy]phenyl}-1- (ESI(+)) (pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 472 (M + H)⁺ 800 (3S)-N-(4-{[1-(4-fluorobenzoyl)piperidin-4-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 490 (M + H)⁺ 801 (3S)-N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxy} (ESI(+)) phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide m/e 452 (M + H)⁺ 802 (3S)-N-[4-({1-[(2-methylcyclopropyl)carbonyl]piperidin-4- (ESI(+)) yl}oxy)phenyl]-1-(pyridazin-3-yl)pyrrolidine-3- m/e 450 carboxamide (M + H)⁺

Example 803 N-{4-[5-(2,2-dimethylpropyl)-1,3,4-oxadiazol-2-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide Example 803A N′-(3,3-dimethylbutanoyl)-4-nitrobenzohydrazide

A suspension of 4-nitrobenzohydrazide (0.500 g, 2.76 mmol), and 4-methylmorpholine (0.455 ml, 4.14 mmol) were stirred in dichloromethane (20 ml). 3,3-Dimethylbutanoyl chloride (0.422 ml, 3.04 mmol) was added and the reaction mixture was stirred for 2 hours. Normal phase chromatography of the crude reaction mixture gave the title compound.

Example 803B 2-neopentyl-5-(4-nitrophenyl)-1,3,4-oxadiazole

A mixture of N′-(3,3-dimethylbutanoyl)-4-nitrobenzohydrazide (0.556 g, 1.991 mmol) and methyl N-(triethylammoniumsulfonyl)carbamate (0.572 g, 2.389 mmol) in tetrahydrofuran (10 ml) was heated to 120° C. in a microwave for 45 minutes. The crude reaction mixture was concentrated and purified by normal phase chromatography to give the title compound.

Example 803C 4-(5-neopentyl-1,3,4-oxadiazol-2-yl)aniline

The title compound was prepared as described in Example 1B, substituting 2-neopentyl-5-(4-nitrophenyl)-1,3,4-oxadiazole for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 803D N-{4-[5-(2,2-dimethylpropyl)-1,3,4-oxadiazol-2-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting 4-(5-neopentyl-1,3,4-oxadiazol-2-yl)aniline for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 1-(pyridazin-3-yl)azetidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.45 (s, 1H), 8.57 (dd, J=4.5, 1.3 Hz, 1H), 7.97-7.91 (m, 2H), 7.88-7.82 (m, 2H), 7.39 (dd, J=9.0, 4.5 Hz, 1H), 6.84 (dd, J=9.0, 1.4 Hz, 1H), 4.26 (t, J=8.4 Hz, 2H), 4.18 (dd, J=8.2, 5.9 Hz, 2H), 3.79 (tt, J=8.6, 5.9 Hz, 1H), 2.82 (s, 2H), 1.03 (s, 9H); MS (ESI(+)) m/e 393 (M+H)⁺.

Example 804 N-{4-[1-(2,2-dimethylpropyl)-1H-imidazol-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide Example 804A 1-neopentyl-4-(4-nitrophenyl)-1H-imidazole

To a solution of 4-(4-nitrophenyl)-1H-imidazole (0.500 g, 2.64 mmol) in N,N-dimethylformamide (10 ml) was added cesium carbonate (1.292 g, 3.96 mmol) followed by 1-bromo-2,2-dimethylpropane (0.366 ml, 2.91 mmol). After heating at 85° overnight, the reaction mixture was cooled to room temperature, diluted with ethyl acetate, washed with water and brine, dried over magnesium sulfate, filtered and concentrated. Normal phase chromatography provided the title compound.

Example 804B 4-(1-neopentyl-1H-imidazol-4-yl)aniline

The title compound was prepared as described in Example 1B, substituting 1-neopentyl-4-(4-nitrophenyl)-1H-imidazole for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 804C N-{4-[1-(2,2-dimethylpropyl)-1H-imidazol-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting 4-(1-neopentyl-1H-imidazol-4-yl)aniline for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 1-(pyridazin-3-yl)azetidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.08 (s, 1H), 8.56 (dd, J=4.6, 1.3 Hz, 1H), 7.73-7.66 (m, 2H), 7.64-7.58 (m, 2H), 7.57 (d, J=1.2 Hz, 1H), 7.49 (d, J=1.1 Hz, 1H), 7.38 (dd, J=9.0, 4.5 Hz, 1H), 6.83 (dd, J=9.0, 1.4 Hz, 1H), 4.25 (t, J=8.3 Hz, 2H), 4.16 (dd, J=8.1, 6.0 Hz, 2H), 3.77 (s, 2H), 3.77-3.69 (m, 1H), 0.91 (s, 9H); MS (ESI(+)) m/e 391 (M+H)⁺.

Example 805 N-[4-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide Example 805A 3-cyclopropyl-1-(4-nitrophenyl)prop-2-yn-1-one

A 250-mL round bottom flask was charged with bis(triphenylphosphine)palladium bischloride (151 mg, 0.216 mmol) and copper iodide (82 mg, 0.431 mmol), and the flask was degassed with nitrogen. Tetrahydrofuran (40 mL) was added through a septum, and nitrogen was bubbled through the mixture for 30 minutes. To this was added dropwise a nitrogen-degassed solution of 4-nitrobenzoyl chloride (2 g, 10.8 mmol), ethynylcyclopropane (784 mg, 11.9 mmol) and triethylamine (1.31 g, 12.9 mmol) in tetrahydrofuran (15 mL). The reaction mixture was stirred at room temperature for 2 hours and then concentrated to dryness. The residue was purified by normal phase chromatography to give the title compound.

Example 805B 3-cyclopropyl-1-methyl-5-(4-nitrophenyl)-1H-pyrazole

3-Cyclopropyl-1-(4-nitrophenyl)prop-2-yn-1-one (500 mg, 2.323 mmol) was dissolved in N,N-dimethylformamide (7.75 mL), and the solution was chilled to 0° C. Methylhydrazine (118 mg, 2.56 mmol) was added dropwise. The mixture was stirred overnight at room temperature then diluted with water (25 mL) and stirred for 45 minutes.

The resulting precipitate was collected by filtration to give the title compound.

Example 805C 4-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)aniline

The title compound was prepared as described in Example 1B, substituting 3-cyclopropyl-1-methyl-5-(4-nitrophenyl)-1H-pyrazole for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 805D N-[4-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting 4-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)aniline for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 1-(pyridazin-3-yl)azetidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ 10.11 (s, 1H), 8.56 (dd, J=4.5, 1.3 Hz, 1H), 7.69-7.58 (m, 4H), 7.38 (dd, J=9.0, 4.5 Hz, 1H), 6.83 (dd, J=9.0, 1.3 Hz, 1H), 6.28 (s, 1H), 4.25 (t, J=8.3 Hz, 2H), 4.16 (dd, J=8.1, 6.0 Hz, 2H), 3.84 (s, 3H), 3.75 (dq, J=8.3, 5.9 Hz, 1H), 1.95-1.82 (m, 1H), 1.02-0.92 (m, 2H), 0.71-0.62 (m, 2H); MS (ESI(+)) m/e 375 (M+H)⁺.

Example 806 N-{4-[5-(2,2-dimethylpropyl)-1,2,4-oxadiazol-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide Example 806A 5-neopentyl-3-(4-nitrophenyl)-1,2,4-oxadiazole

To a suspension of (Z)-N′-hydroxy-4-nitrobenzimidamide (0.500 g, 2.76 mmol) in dichloromethane (6 ml) was added 4-methylmorpholine (0.455 ml, 4.14 mmol) followed by 3,3-dimethylbutanoyl chloride (0.422 ml, 3.04 mmol). After 1 hour, the crude reaction mixture was purified by normal phase chromatography and the collected intermediate was dissolved in dichloromethane (8 ml) and treated with tetrabutylammonium fluoride (1.0M in THF) (8.28 ml, 8.28 mmol). After 3 hours at room temperature, the mixture was diluted with ethyl acetate, washed with water, dried over magnesium sulfate, filtered, and concentrated. Normal phase chromatography provided the title compound.

Example 806B 4-(5-neopentyl-1,2,4-oxadiazol-3-yl)aniline

The title compound was prepared as described in Example 1B, substituting 5-neopentyl-3-(4-nitrophenyl)-1,2,4-oxadiazole for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 806C N-{4-[5-(2,2-dimethylpropyl)-1,2,4-oxadiazol-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting 4-(5-neopentyl-1,2,4-oxadiazol-3-yl)aniline for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 1-(pyridazin-3-yl)azetidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.40 (s, 1H), 8.57 (dd, J=4.6, 1.3 Hz, 1H), 8.05-7.89 (m, 2H), 7.89-7.75 (m, 2H), 7.38 (dd, J=9.0, 4.5 Hz, 1H), 6.84 (dd, J=9.0, 1.3 Hz, 1H), 4.26 (t, J=8.4 Hz, 2H), 4.18 (dd, J=8.1, 5.9 Hz, 2H), 3.79 (tt, J=8.5, 5.9 Hz, 1H), 2.90 (s, 2H), 1.04 (s, 9H); MS (ESI(+)) m/e 393 (M+H)⁺.

Example 807 N-{4-[3-cyclopropyl-1-(2-methoxyethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 805, substituting (2-methoxyethyl)hydrazine for methylhydrazine in Example 805B. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.20 (s, 1H), 8.56 (d, J=4.5 Hz, 1H), 7.72-7.57 (m, 4H), 7.55-7.48 (m, 1H), 7.07-6.99 (m, 1H), 6.28 (s, 1H), 4.38-4.18 (m, 6H), 3.83-3.69 (m, 3H), 3.25 (s, 3H), 1.98-1.87 (m, 1H), 1.00-0.91 (m, 2H), 0.67 (d, J=2.3 Hz, 2H); MS (ESI(+)) m/e 419 (M+H)⁺.

Example 808 tert-butyl 4-(5-{[1-(pyridazin-3-yl)azetidin-3-yl]carbamoyl}thiophen-2-yl)piperidine-1-carboxylate Example 808A tert-butyl (1-(6-chloropyridazin-3-yl)azetidin-3-yl)carbamate

The title compound was prepared as described in Example 147A, substituting tert-butyl azetidin-3-ylcarbamate for tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate.

Example 808B tert-butyl (1-(pyridazin-3-yl)azetidin-3-yl)carbamate

The title compound was prepared as described in Example 147B, substituting tert-butyl (1-(6-chloropyridazin-3-yl)azetidin-3-yl)carbamate for 4-(4-(1-(6-chloropyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate.

Example 808C 1-(pyridazin-3-yl)azetidin-3-amine

The title compound was prepared as described in Example 1D, substituting tert-butyl (1-(pyridazin-3-yl)azetidin-3-yl)carbamate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 808D tert-butyl 4-(5-{[1-(pyridazin-3-yl)azetidin-3-yl]carbamoyl}thiophen-2-yl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting 1-(pyridazin-3-yl)azetidin-3-amine for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)thiophene-2-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 8.95 (d, J=7.2 Hz, 1H), 8.56 (dd, J=4.5, 1.3 Hz, 1H), 7.65 (d, J=3.8 Hz, 1H), 7.38 (dd, J=8.9, 4.5 Hz, 1H), 6.95 (dd, J=3.8, 0.8 Hz, 1H), 6.83 (dd, J=9.0, 1.4 Hz, 1H), 4.92-4.77 (m, 1H), 4.36 (t, J=8.1 Hz, 2H), 4.05-3.97 (m, 4H), 3.09-2.66 (m, 3H), 1.98-1.88 (m, 2H), 1.40 (s, 11H); MS (ESI(+)) m/e 444 (M+H)⁺.

Example 809 tert-butyl 4-fluoro-4-[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]piperidine-1-carboxylate Example 809A tert-butyl 4-(4-aminophenyl)-4-hydroxypiperidine-1-carboxylate

N-(4-Bromophenyl)-1,1,1-trimethyl-N-(trimethylsilyl)silanamine (7 g, 22.12 mmol) in tetrahydrofuran (100 mL) was treated with a solution of n-BuLi (1M, 22 mL) at −78° C. The reaction mixture was stirred an additional hour at −78° C. and then treated with a solution of tert-butyl 4-oxopiperidine-1-carboxylate (3.97 g, 19.91 mmol) in tetrahydrofuran (20 mL). The reaction mixture was stirred at −78° C. for 30 minutes and then warmed to room temperature. The reaction was quenched by addition of saturated ammonium chloride solution (100 mL) and then was extracted with ethyl acetate. The combined organics were washed with water, brine, dried with magnesium sulfate, filtered and concentrated. The crude tert-butyl 4-(4-(bis(trimethylsilyl)amino)phenyl)-4-hydroxypiperidine-1-carboxylate was treated with a solution of tetrabutylammonium fluoride (1M THF, 40 mL) at room temperature for 1 hour. The reaction mixture was diluted with water and extracted with ethyl acetate. The organics were washed with water and brine, dried with magnesium sulfate, filtered and concentrated. Purification by normal phase chromatography provided the title compound.

Example 809B tert-butyl 4-(4-(1-((benzyloxy)carbonyl)azetidine-3-carboxamido)phenyl)-4-hydroxypiperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting tert-butyl 4-(4-aminophenyl)-4-hydroxypiperidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 1-((benzyloxy)carbonyl)azetidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 809C tert-butyl 4-(4-(1-((benzyloxy)carbonyl)azetidine-3-carboxamido)phenyl)-4-fluoropiperidine-1-carboxylate

tert-Butyl 4-(4-(1-((benzyloxy)carbonyl)azetidine-3-carboxamido)phenyl)-4-hydroxypiperidine-1-carboxylate (2.5 g, 4.91 mmol) in 50 mL dichloromethane was cooled to −78° C. and diethylaminosulfur trifluoride was added dropwise via a syringe. The reaction solution was stirred at −78° C. for an additional 1 hour and then warmed to 0° C. The reaction was allowed to stir at 0° C. for 1 hour and was cooled back down to −78° C. The reaction mixture was diluted with 50 mL of dichloromethane followed by quenching with 10 mL methanol. The solution was washed with saturated sodium bicarbonate and brine, dried with magnesium sulfate and filtered. Concentration and normal phase chromatography provided the title compound.

Example 809D tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)-4-fluoropiperidine-1-carboxylate

The title compound was prepared as described in Example 1B, substituting tert-butyl 4-(4-(1-((benzyloxy)carbonyl)azetidine-3-carboxamido)phenyl)-4-fluoropiperidine-1-carboxylate for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 809E tert-butyl 4-(4-(1-(6-chloropyridazin-3-yl)azetidine-3-carboxamido)phenyl)-4-fluoropiperidine-1-carboxylate

The title compound was prepared as described in Example 147A, substituting tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)-4-fluoropiperidine-1-carboxylate for tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate.

Example 809F tert-butyl 4-fluoro-4-[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]piperidine-1-carboxylate

The title compound was prepared as described in Example 147B, substituting tert-butyl 4-(4-(1-(6-chloropyridazin-3-yl)azetidine-3-carboxamido)phenyl)-4-fluoropiperidine-1-carboxylate for 4-(4-(1-(6-chloropyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.18-10.08 (m, 1H), 8.55 (dd, J=4.5, 1.4 Hz, 1H), 7.65-7.56 (m, 2H), 7.40-7.33 (m, 3H), 6.82 (dd, J=8.9, 1.4 Hz, 1H), 4.23 (t, J=8.3 Hz, 2H), 4.14 (dd, J=8.2, 5.7 Hz, 2H), 4.08-3.91 (m, 2H), 3.81-3.68 (m, 1H), 3.17-2.70 (m, 2H), 2.07-1.82 (m, 3H), 1.42-1.35 (s, 10H); MS (ESI(+)) m/e 456 (M+H)⁺.

Example 810 5-(1-benzoylpiperidin-4-yl)-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide Example 810A 5-(piperidin-4-yl)-N-(1-(pyridazin-3-yl)azetidin-3-yl)thiophene-2-carboxamide

The title compound was prepared as described in Example 1D, substituting tert-butyl 4-(5-{[1-(pyridazin-3-yl)azetidin-3-yl]carbamoyl}thiophen-2-yl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 810B 5-(1-benzoylpiperidin-4-yl)-N-[1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2-carboxamide

The title compound was prepared as described in Example 1A, substituting 5-(piperidin-4-yl)-N-(1-(pyridazin-3-yl)azetidin-3-yl)thiophene-2-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and benzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 8.96 (d, J=7.2 Hz, 1H), 8.56 (dd, J=4.5, 1.3 Hz, 1H), 7.66 (d, J=3.8 Hz, 1H), 7.51-7.34 (m, 6H), 6.98 (dd, J=3.8, 0.8 Hz, 1H), 6.84 (dd, J=9.0, 1.4 Hz, 1H), 4.92-4.77 (m, 1H), 4.6 (bs, 1H), 4.36 (t, J=8.1 Hz, 2H), 4.01 (dd, J=8.6, 5.6 Hz, 2H), 3.64 (bs, 1H), 3.23-2.83 (m, 3H), 2.10-1.84 (m, 2H), 1.67-1.48 (m, 2H); MS (ESI(+)) m/e 448 (M+H)⁺.

The following Examples were essentially prepared as described in Example 810, substituting an appropriate carboxylic acid in Example 810B.

TABLE 19 Ex Name MS 811 5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-[1- (ESI(+)) (pyridazin-3-yl)azetidin-3-yl]thiophene-2- m/e 466 carboxamide (M + H)⁺ 812 5-[1-(2-methylbenzoyl)piperidin-4-yl]-N-[1- (ESI(+)) (pyridazin-3-yl)azetidin-3-yl]thiophene-2- m/e 462 carboxamide (M + H)⁺ 813 5-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-N-[1- (ESI(+)) (pyridazin-3-yl)azetidin-3-yl]thiophene-2- m/e 484 carboxamide (M + H)⁺ 814 5-[1-(3-fluorobenzoyl)piperidin-4-yl]-N-[1- (ESI(+)) (pyridazin-3-yl)azetidin-3-yl]thiophene-2- m/e 466 carboxamide (M + H)⁺ 815 5-[1-(4-fluorobenzoyl)piperidin-4-yl]-N-[1- (ESI(+)) (pyridazin-3-yl)azetidin-3-yl]thiophene-2- m/e 466 carboxamide (M + H)⁺ 816 5-[1-(3,5-difluorobenzoyl)piperidin-4-yl]-N-[1- (ESI(+)) (pyridazin-3-yl)azetidin-3-yl]thiophene-2- m/e 484 carboxamide (M + H)⁺ 847 5-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-N-[1- (ESI(+)) (pyridazin-3-yl)azetidin-3-yl]thiophene-2- m/e 428 carboxamide (M + H)⁺ 848 5-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}-N- (ESI(+)) [1-(pyridazin-3-yl)azetidin-3-yl]thiophene-2- m/e 426 carboxamide (M + H)⁺ 849 N-[1-(pyridazin-3-yl)azetidin-3-yl]-5-[1-(3,3,3- (ESI(+)) trifluoropropanoyl)piperidin-4-yl]thiophene-2- m/e 454 carboxamide (M + H)⁺ 850 5-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]-N-[1- (ESI(+)) (pyridazin-3-yl)azetidin-3-yl]thiophene-2- m/e 442 carboxamide (M + H)⁺ 855 N-[1-(pyridazin-3-yl)azetidin-3-yl]-5-[1-(4,4,4- (ESI(+)) trifluorobutanoyl)piperidin-4-yl]thiophene-2- m/e 468 carboxamide (M + H)⁺ 856 5-[1-(cyclopropylcarbonyl)piperidin-4-yl]-N-[1- (ESI(+)) (pyridazin-3-yl)azetidin-3-yl]thiophene-2- m/e 412 carboxamide (M + H)⁺

Example 817 N-{4-[3-cyclopropyl-1-(2-hydroxyethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 805, substituting 2-hydrazinylethanol for methylhydrazine in 805B. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.14 (s, 1H), 8.56 (dd, J=4.5, 1.3 Hz, 1H), 7.72-7.58 (m, 4H), 7.38 (dd, J=9.0, 4.5 Hz, 1H), 6.83 (dd, J=9.0, 1.4 Hz, 1H), 6.27 (s, 1H), 4.90 (br s, 1H), 4.31-4.08 (m, 6H), 3.84-3.69 (m, 3H), 2.01-1.88 (m, 1H), 1.01-0.89 (m, 2H), 0.72-0.62 (m, 2H); MS (ESI(+)) m/e 405 (M+H)⁺.

Example 818 N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide Example 818A tert-butyl 4-(4-(1-((benzyloxy)carbonyl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting tert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 1-((benzyloxy)carbonyl)azetidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 818B tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1B, substituting tert-butyl 4-(4-(1-((benzyloxy)carbonyl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 818C tert-butyl 4-(4-(1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 147A, substituting tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate and 3,6-difluoropyridazine for 3,6-dichloropyridazine.

Example 818D 1-(6-fluoropyridazin-3-yl)-N-(4-(piperidin-4-yl)phenyl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting tert-butyl 4-(4-(1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 818E N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting 1-(6-fluoropyridazin-3-yl)-N-(4-(piperidin-4-yl)phenyl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and benzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.03 (s, 1H), 7.54 (d, J=8.6 Hz, 2H), 7.49-7.38 (m, 6H), 7.22 (d, J=8.6 Hz, 2H), 7.12 (dd, J=9.5, 6.8 Hz, 1H), 4.23 (t, J=8.3 Hz, 2H), 4.14 (dd, J=8.0, 6.0 Hz, 2H), 3.71 (ddd, J=14.4, 8.4, 5.9 Hz, 2H), 2.86 (dd, J=67.9, 55.9 Hz, 3H), 2.04-1.43 (m, 4H); MS (ESI(+)) m/e 460 (M+H)⁺.

Example 819 N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting 1-(6-fluoropyridazin-3-yl)-N-(4-(piperidin-4-yl)phenyl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2-fluorobenzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.04 (s, 1H), 7.58-7.34 (m, 5H), 7.35-7.25 (m, 2H), 7.23-7.17 (m, 2H), 7.12 (dd, J=9.4, 6.7 Hz, 1H), 4.70-4.61 (m, 1H), 4.23 (t, J=8.3 Hz, 2H), 4.14 (d, J=13.9 Hz, 2H), 3.77-3.66 (m, 1H), 3.50-3.41 (m, 1H), 3.23-3.09 (m, 1H), 2.95-2.72 (m, 2H), 1.91-1.82 (m, 1H), 1.79-1.42 (m, 3H); MS (ESI(+)) m/e 478 (M+H)⁺.

Example 820 N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting 1-(6-fluoropyridazin-3-yl)-N-(4-(piperidin-4-yl)phenyl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2,2-dimethylpropanoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.03 (s, 1H), 7.57-7.50 (m, 2H), 7.41 (dd, J=9.4, 1.9 Hz, 1H), 7.22-7.15 (m, 2H), 7.12 (dd, J=9.4, 6.7 Hz, 1H), 4.45-4.36 (m, 2H), 4.23 (t, J=8.3 Hz, 2H), 4.14 (dd, J=8.0, 5.9 Hz, 2H), 3.77-3.66 (m, 1H), 2.93-2.66 (m, 3H), 1.82-1.74 (m, 2H), 1.52-1.35 (m, 2H), 1.22 (s, 9H); MS (ESI(+)) m/e 440 (M+H)⁺.

Example 821 1-(6-fluoropyridazin-3-yl)-N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting 1-(6-fluoropyridazin-3-yl)-N-(4-(piperidin-4-yl)phenyl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and isobutyric acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.03 (s, 1H), 7.54 (d, J=8.5 Hz, 2H), 7.41 (dd, J=9.5, 1.9 Hz, 1H), 7.18 (d, J=8.5 Hz, 2H), 7.12 (dd, J=9.5, 6.8 Hz, 1H), 4.62-4.45 (m, 1H), 4.23 (t, J=8.3 Hz, 2H), 4.14 (dd, J=7.9, 6.1 Hz, 2H), 4.10-3.97 (m, 1H), 3.72 (ddd, J=8.4, 7.2, 4.2 Hz, 1H), 3.10 (s, 1H), 2.89 (dt, J=13.4, 6.7 Hz, 1H), 2.81-2.64 (m, 1H), 2.57 (s, 1H), 1.79 (ddd, J=16.4, 10.0, 2.9 Hz, 2H), 1.58-1.25 (m, 2H), 1.12-0.92 (m, 6H); MS (ESI(+)) m/e 426 (M+H)⁺.

Example 822 N-{4-[1-(2-ethylbutanoyl)piperidin-4-yl]phenyl}-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting 1-(6-fluoropyridazin-3-yl)-N-(4-(piperidin-4-yl)phenyl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2-ethylbutanoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.03 (s, 1H), 7.57-7.51 (m, 2H), 7.41 (dd, J=9.4, 1.9 Hz, 1H), 7.21-7.08 (m, 3H), 4.68-4.59 (m, 1H), 4.31-4.06 (m, 1H), 3.77-3.66 (m, 1H), 3.15-3.04 (m, 1H), 2.66 (ddt, J=25.3, 20.0, 12.2 Hz, 1H), 1.87-1.74 (m, 2H), 1.64-1.27 (m, 6H), 0.87-0.76 (m, 6H); MS (ESI(+)) m/e 454 (M+H)⁺.

Example 823 N-{4-[1-(4-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(6-fluoropyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting 1-(6-fluoropyridazin-3-yl)-N-(4-(piperidin-4-yl)phenyl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 4-fluorobenzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.04 (s, 1H), 7.59-7.46 (m, 4H), 7.41 (dd, J=9.4, 1.9 Hz, 1H), 7.32-7.17 (m, 4H), 7.13 (dd, J=9.4, 6.7 Hz, 1H), 4.70-4.48 (m, 1H), 4.24 (t, J=8.3 Hz, 2H), 4.14 (dd, J=8.0, 5.9 Hz, 2H), 4.06-3.53 (m, 2H), 3.22-2.68 (m, 3H), 2.04-1.50 (m, 4H); MS (ESI(+)) m/e 478 (M+H)⁺.

Example 824 (3S)—N-(4-{[(3S)-1-benzoylpyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide Example 824A (S)-tert-butyl 3-(4-((S)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamido)phenoxy)pyrrolidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting (R)-tert-butyl 3-(4-aminophenoxyl)pyrrolidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and (S)-1-(pyridazin-3-yl)pyrrolidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 824B (S)-1-(pyridazin-3-yl)-N-(4-((S)-pyrrolidin-3-yloxy)phenyl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting (S)-tert-butyl 3-(4-((S)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamido)phenoxy)pyrrolidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 774C (3S)—N-(4-{[(3S)-1-benzoylpyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting (S)-1-(pyridazin-3-yl)-N-(4-((S)-pyrrolidin-3-yloxy)phenyl)pyrrolidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and benzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.04-9.95 (m, 1H), 8.51-8.45 (m, 1H), 7.61-7.37 (m, 7H), 7.37-7.30 (m, 1H), 6.99-6.92 (m, 1H), 6.90-6.83 (m, 2H), 5.07-4.92 (m, 1H), 3.88-3.70 (m, 2H), 3.71-3.38 (m, 6H), 2.37-1.97 (m, 4H); MS (ESI(+)) m/e 458 (M+H)⁺.

Example 825 (3S)—N-(4-{[(3S)-1-(2-fluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting (S)-1-(pyridazin-3-yl)-N-(4-((S)-pyrrolidin-3-yloxy)phenyl)pyrrolidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2-fluorobenzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.04-9.96 (m, 1H), 8.48 (d, J=4.5 Hz, 1H), 7.59-7.37 (m, 4H), 7.37-7.22 (m, 3H), 6.94 (d, J=8.7 Hz, 1H), 6.87 (dd, J=8.9, 4.4 Hz, 2H), 3.86-3.52 (m, 5H), 3.54-3.37 (m, 2H), 2.37-1.97 (m, 4H); MS (ESI(+)) m/e 476 (M+H)⁺.

Example 826 (3S)—N-(4-{[(3S)-1-(3,5-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting (S)-1-(pyridazin-3-yl)-N-(4-((S)-pyrrolidin-3-yloxy)phenyl)pyrrolidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2,4-fluorobenzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.07-9.93 (m, 1H), 8.47 (t, J=4.6 Hz, 1H), 7.54 (dt, J=12.8, 10.3 Hz, 2H), 7.44-7.18 (m, 4H), 7.02-6.80 (m, 3H), 5.16-4.85 (m, 1H), 3.91-3.70 (m, 2H), 3.70-3.35 (m, 7H), 2.43-1.97 (m, 4H); MS (ESI(+)) m/e 494 (M+H)⁺.

Example 827 (3S)—N-(4-{[(3S)-1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(pyridazin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting (S)-1-(pyridazin-3-yl)-N-(4-((S)-pyrrolidin-3-yloxy)phenyl)pyrrolidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2,2-dimethylpropanoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 9.99 (s, 1H), 8.48 (dd, J=4.5, 1.3 Hz, 1H), 7.57-7.50 (m, 2H), 7.33 (dd, J=9.1, 4.5 Hz, 1H), 6.95-6.83 (m, 4H), 4.95 (bs, 1H), 3.86-3.39 (m, 8H), 2.39-1.92 (m, 4H), 1.15 (s, 9H); MS (ESI(+)) m/e 438. (M+H)⁺.

Example 828 N-{2-fluoro-4[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide Example 828A tert-butyl 4-(4-amino-3-fluorophenyl)-5,6-dihydropyridine-1(2H)-carboxylate

The title compound was prepared as described in Example 148A, substituting tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 4-bromo-2-fluoroaniline for 4-bromoaniline.

Example 828B tert-butyl 4-(4-amino-3-fluorophenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1B, substituting tert-butyl 4-(4-amino-3-fluorophenyl)-5,6-dihydropyridine-1(2H)-carboxylate for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 828C tert-butyl 4-(4-(1-((benzyloxy)carbonyl)azetidine-3-carboxamido)-3-fluorophenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting tert-butyl 4-(4-amino-3-fluorophenyl)piperidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 1-((benzyloxy)carbonyl)azetidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 828D tert-butyl 4-(4-(azetidine-3-carboxamido)-3-fluorophenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1B, substituting tert-butyl 4-(4-(1-((benzyloxy)carbonyl)azetidine-3-carboxamido)-3-fluorophenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 828E tert-butyl 4-(4-(1-(6-chloropyridazin-3-yl)azetidine-3-carboxamido)-3-fluorophenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 147A, substituting tert-butyl 4-(4-(azetidine-3-carboxamido)-3-fluorophenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate.

Example 828F tert-butyl 4-(3-fluoro-4-(1-(pyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 147B, substituting tert-butyl 4-(4-(1-(6-chloropyridazin-3-yl)azetidine-3-carboxamido)-3-fluorophenyl)piperidine-1-carboxylate for 4-(4-(1-(6-chloropyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate.

Example 828G N-(2-fluoro-4-(piperidin-4-yl)phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting tert-butyl 4-(3-fluoro-4-(1-(pyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 828H N-{2-fluoro-4[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(2-fluoro-4-(piperidin-4-yl)phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2-fluorobenzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 9.86 (s, 1H), 8.56 (dd, J=4.5, 1.3 Hz, 1H), 7.79 (t, J=8.3 Hz, 1H), 7.58-7.41 (m, 2H), 7.42-7.25 (m, 3H), 7.23-7.14 (m, 1H), 7.11-7.03 (m, 1H), 6.83 (dd, J=9.0, 1.4 Hz, 1H), 4.70-4.61 (m, 1H), 4.24 (t, J=8.3 Hz, 2H), 4.14 (dd, J=8.1, 5.8 Hz, 2H), 3.92-3.81 (m, 1H), 3.51-3.42 (m, 1H), 3.23-3.10 (m, 1H), 2.92-2.76 (m, 2H), 1.94-1.81 (m, 1H), 1.83-1.44 (m, 3H); MS (ESI(+)) m/e 478 (M+H)⁺.

The following Examples were essentially prepared as described in Example 828, substituting the appropriate carboxylic acid in Example 828H.

TABLE 20 Ex Name MS 829 N-[4-(1-benzoylpiperidin-4-yl)-2-fluorophenyl]-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 460 (M + H)⁺ 830 N-{2-fluoro-4-[1-(3-fluorobenzoyl)piperidin-4-yl] (ESI(+)) phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 478 (M + H)⁺ 831 N-{2-fluoro-4-[1-(2-methylbenzoyl)piperidin-4-yl] (ESI(+)) phenyl}-1-(pyridazin-3-yl)azetidine-3- m/e 474 carboxamide (M + H)⁺ 832 N-{2-fluoro-4-[1-(4-fluorobenzoyl)piperidin-4-yl] (ESI(+)) phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 478 (M + H)⁺ 833 N-{4-[1-(2,4-difluorobenzoyl)piperidin-4-yl]-2- (ESI(+)) fluorophenyl}-1-(pyridazin-3-yl)azetidine-3- m/e 496 carboxamide (M + H)⁺ 834 N-{4-[1-(3,5-difluorobenzoyl)piperidin-4-yl]-2- (ESI(+)) fluorophenyl}-1-(pyridazin-3-yl)azetidine-3- m/e 460 carboxamide (M + H)⁺ 835 N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-2- (ESI(+)) fluorophenyl}-1-(pyridazin-3-yl)azetidine-3- m/e 454 carboxamide (M + H)⁺ 858 N-{2-fluoro-4-[1-(2-methylpropanoyl)piperidin-4-yl] (ESI(+)) phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 426 (M + H)⁺ 859 N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-2- (ESI(+)) fluorophenyl}-1-(pyridazin-3-yl)azetidine-3- m/e 440 carboxamide (M + H)⁺ 860 N-{4-[1-(cyclopropylcarbonyl)piperidin-4-yl]-2- (ESI(+)) fluorophenyl}-1-(pyridazin-3-yl)azetidine-3- m/e 424 carboxamide (M + H)⁺ 861 N-(2-fluoro-4-{1-[(1-methylcyclopropyl)carbonyl] (ESI(+)) piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine- m/e 438 3-carboxamide (M + H)⁺ 862 N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]-2- (ESI(+)) fluorophenyl}-1-(pyridazin-3-yl)azetidine- m/e 438 3-carboxamide (M + H)⁺

Example 836 (3S)—N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide Example 836A (S)-tert-butyl 4-(4-(1-((benzyloxy)carbonyl)pyrrolidine-3-carboxamido)phenoxy)piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting (S)-1-benzyl 3-tert-butyl pyrrolidine-1,3-dicarboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 836B (S)-tert-butyl 4-(4-(pyrrolidine-3-carboxamido)phenoxy)piperidine-1-carboxylate

The title compound was prepared as described in Example 1B, substituting (S)-tert-butyl 4-(4-(1-((benzyloxy)carbonyl)pyrrolidine-3-carboxamido)phenoxy)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 836C (S)-tert-butyl 4-(4-(1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamido)phenoxy)piperidine-1-carboxylate

The title compound was prepared as described in Example 1C, substituting 3-bromo-6-methylpyridazine for 3-bromopyridine and (S)-tert-butyl 4-(4-(pyrrolidine-3-carboxamido)phenoxy)piperidine-1-carboxylate for tert-butyl 4-(4-(azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 836D (S)-1-(6-methylpyridazin-3-yl)-N-(4-(piperidin-4-yloxy)phenyl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting (S)-tert-butyl 4-(4-(1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamido)phenoxy)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 836E (3S)—N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting (S)-1-(6-methylpyridazin-3-yl)-N-(4-(piperidin-4-yloxy)phenyl)pyrrolidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2-fluorobenzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 9.98 (s, 1H), 7.57-7.45 (m, 3H), 7.42 (td, J=7.2, 1.8 Hz, 1H), 7.35-7.20 (m, 3H), 6.98-6.91 (m, 2H), 6.83 (d, J=9.1 Hz, 1H), 4.63-4.54 (m, 1H), 4.05-3.95 (m, 1H), 3.74 (dd, J=10.3, 7.9 Hz, 1H), 3.64-3.42 (m, 3H), 3.31-3.03 (m, 3H), 2.40 (s, 3H), 2.36-2.08 (m, 2H), 2.07-1.76 (m, 2H), 1.78-1.19 (m, 4H); MS (ESI(+)) m/e 504 (M+H)⁺.

Example 837 (3S)—N-{4-[(1-benzoylpiperidin-4-yl)oxy]phenyl}-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting (S)-1-(6-methylpyridazin-3-yl)-N-(4-(piperidin-4-yloxy)phenyl)pyrrolidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and benzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 9.98 (s, 1H), 7.55-7.48 (m, 2H), 7.48-7.37 (m, 5H), 7.23 (d, J=9.1 Hz, 1H), 6.97-6.91 (m, 2H), 6.83 (d, J=9.1 Hz, 1H), 4.57 (dq, J=7.7, 3.8 Hz, 1H), 4.04-3.42 (m, 8H), 3.26 (p, J=7.4 Hz, 1H), 2.41 (s, 3H), 2.35-2.08 (m, 2H), 2.09-1.84 (m, 2H), 1.68-1.51 (m, 2H); MS (ESI(+)) m/e 486 (M+H)⁺.

Example 838 (3S)—N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting (S)-1-(6-methylpyridazin-3-yl)-N-(4-(piperidin-4-yloxy)phenyl)pyrrolidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2,2-dimethylpropanoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 9.98 (s, 1H), 7.55-7.48 (m, 2H), 7.24 (d, J=9.1 Hz, 1H), 6.96-6.90 (m, 2H), 6.83 (d, J=9.1 Hz, 1H), 4.59-4.50 (m, 1H), 3.94-3.80 (m, 2H), 3.74 (dd, J=10.3, 7.9 Hz, 1H), 3.65-3.52 (m, 2H), 3.32-3.18 (m, 4H), 2.40 (s, 3H), 2.34-2.08 (m, 2H), 1.97-1.83 (m, 2H), 1.58-1.43 (m, 2H), 1.20 (s, 9H); MS (ESI(+)) m/e 466 (M+H)⁺.

Example 839 (3S)—N-(4-{[1-(cyclohexylcarbonyl)piperidin-4-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting (S)-1-(6-methylpyridazin-3-yl)-N-(4-(piperidin-4-yloxy)phenyl)pyrrolidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and cyclohexanecarboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 9.98 (s, 1H), 7.55-7.48 (m, 2H), 7.24 (d, J=9.1 Hz, 1H), 6.97-6.90 (m, 2H), 6.83 (d, J=9.2 Hz, 1H), 4.52 (dq, J=7.8, 3.9 Hz, 1H), 3.89-3.66 (m, 3H), 3.68-3.49 (m, 2H), 3.45-3.13 (m, 3H), 2.61-2.55 (m, 1H), 2.40 (s, 3H), 2.36-2.11 (m, 2H), 2.04-1.80 (m, 2H), 1.74-1.08 (m, 13H); MS (ESI(+)) m/e 492 (M+H)⁺.

Example 840 N-{4[8-(2-methylpropanoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide Example 840A tert-butyl 3-(4-nitrophenyl)-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylate

The title compound was prepared as described in Example 148A, substituting 2,2-dimethyl-1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-8-azabicyclo[3.2.1]oct-3-en-8-yl)propan-1-one for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 1-bromo-4-nitrobenzene for 4-bromoaniline.

Example 840B tert-butyl 3-(4-aminophenyl)-8-azabicyclo[3.2.1]octane-8-carboxylate

The title compound was prepared as described in Example 1B, substituting tert-butyl 3-(4-nitrophenyl)-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylate for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 840C tert-butyl 3-(4-(1-((benzyloxy)carbonyl)azetidine-3-carboxamido)phenyl)-8-azabicyclo[3.2.1]octane-8-carboxylate

The title compound was prepared as described in Example 1A, substituting tert-butyl 3-(4-aminophenyl)-8-azabicyclo[3.2.1]octane-8-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 1-((benzyloxy)carbonyl)azetidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 840D tert-butyl 3-(4-(azetidine-3-carboxamido)phenyl)-8-azabicyclo[3.2.1]octane-8-carboxylate

The title compound was prepared as described in Example 1B, substituting tert-butyl 3-(4-(1-((benzyloxy)carbonyl)azetidine-3-carboxamido)phenyl)-8-azabicyclo[3.2.1]octane-8-carboxylate for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 840F tert-butyl 3-(4-(1-(6-chloropyridazin-3-yl)azetidine-3-carboxamido)phenyl)-8-azabicyclo[3.2.1]octane-8-carboxylate

The title compound was prepared as described in Example 147A, substituting tert-butyl 3-(4-(azetidine-3-carboxamido)phenyl)-8-azabicyclo[3.2.1]octane-8-carboxylate for tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate.

Example 840G tert-butyl 3-(4-(1-(pyridazin-3-yl)azetidine-3-carboxamido)phenyl)-8-azabicyclo[3.2.1]octane-8-carboxylate

The title compound was prepared as described in Example 147B, substituting tert-butyl 3-(4-(1-(6-chloropyridazin-3-yl)azetidine-3-carboxamido)phenyl)-8-azabicyclo[3.2.1]octane-8-carboxylate for 4-(4-(1-(6-chloropyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate.

Example 840H N-(4-(8-azabicyclo[3.2.1]octan-3-yl)phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting tert-butyl 3-(4-(1-(pyridazin-3-yl)azetidine-3-carboxamido)phenyl)-8-azabicyclo[3.2.1]octane-8-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 840I N-{4[8-(2-methylpropanoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(4-(8-azabicyclo[3.2.1]octan-3-yl)phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and isobutyric acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.03 (s, 1H), 8.56 (dd, J=4.5, 1.3 Hz, 1H), 7.52 (dd, J=7.4, 3.4 Hz, 2H), 7.37 (dd, J=9.0, 4.5 Hz, 1H), 7.18 (dd, J=17.7, 8.6 Hz, 2H), 6.82 (dd, J=9.0, 1.3 Hz, 1H), 4.51 (ddd, J=15.0, 5.1, 4.4 Hz, 1H), 4.43-4.29 (m, 1H), 4.18 (dt, J=14.0, 8.1 Hz, 4H), 3.72 (ddd, J=8.4, 5.9, 2.5 Hz, 1H), 2.77 (dt, J=13.4, 6.7 Hz, 1H), 2.48-2.14 (m, 3H), 2.04-1.37 (m, 7H), 1.15-0.94 (m, 6H); MS (ESI(+)) m/e 434 (M+H)⁺.

Example 841 1-(pyridazin-3-yl)-N-{4[8-(4,4,4-trifluorobutanoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(4-(8-azabicyclo[3.2.1]octan-3-yl)phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 4,4,4-trifluorobutanoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.03 (d, J=3.6 Hz, 1H), 8.56 (dd, J=4.5, 1.1 Hz, 1H), 7.53 (dd, J=8.6, 2.7 Hz, 2H), 7.37 (dt, J=14.0, 7.0 Hz, 1H), 7.21 (dd, J=23.0, 8.6 Hz, 2H), 6.80 (dd, J=19.3, 8.9 Hz, 1H), 4.61-4.47 (m, 1H), 4.32 (dd, J=16.5, 8.6 Hz, 1H), 4.23 (t, J=8.3 Hz, 2H), 4.14 (t, J=7.0 Hz, 2H), 3.82-3.62 (m, 1H), 3.22-3.04 (m, 1H), 3.04-2.90 (m, 1H), 2.78-2.50 (m, 6H), 2.41-2.12 (m, 1H), 2.05-1.38 (m, 8H); MS (ESI(+)) m/e 488 (M+H)⁺.

Example 842 N-[4-(8-benzoyl-8-azabicyclo[3.2.1]oct-3-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(4-(8-azabicyclo[3.2.1]octan-3-yl)phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and benzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.04 (d, J=2.4 Hz, 1H), 8.56 (dt, J=9.1, 4.5 Hz, 1H), 7.63-7.42 (m, 7H), 7.37 (dt, J=14.0, 7.0 Hz, 1H), 7.29 (d, J=8.5 Hz, 1H), 7.23 (d, J=8.5 Hz, 1H), 6.91-6.70 (m, 1H), 4.69 (d, J=6.1 Hz, 1H), 4.24 (t, J=8.3 Hz, 2H), 4.19-4.11 (m, 2H), 4.01 (d, J=14.9 Hz, 1H), 3.85-3.61 (m, 1H), 2.47-2.22 (m, 1H), 2.02-1.53 (m, 7H); MS (ESI(+)) m/e 468 (M+H)⁺.

Example 843 N-{4[8-(2-fluorobenzoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(4-(8-azabicyclo[3.2.1]octan-3-yl)phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2-fluorobenzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.04 (s, 1H), 8.56 (dd, J=4.5, 1.3 Hz, 1H), 7.59-7.44 (m, 4H), 7.46-7.16 (m, 5H), 6.82 (dd, J=9.0, 1.4 Hz, 1H), 4.73-4.65 (m, 1H), 4.24 (t, J=8.3 Hz, 2H), 4.14 (dd, J=8.0, 5.9 Hz, 2H), 3.81-3.67 (m, 2H), 2.10 (s, 1H), 2.05-1.35 (m, 8H); MS (ESI(+)) m/e 486 (M+H)⁺.

Example 844

-   N-{4-[8-(2,2-dimethylpropanoyl)-8-azabicyclo[3.2.1]oct-3-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(4-(8-azabicyclo[3.2.1]octan-3-yl)phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2,2-dimethylpropanoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.02 (s, 1H), 8.56 (dd, J=4.5, 1.3 Hz, 1H), 7.56-7.49 (m, 2H), 7.38 (dd, J=9.0, 4.5 Hz, 1H), 7.24-7.14 (m, 2H), 6.82 (dd, J=9.0, 1.4 Hz, 1H), 4.66-4.51 (m, 2H), 4.23 (t, J=8.3 Hz, 2H), 4.14 (dd, J=8.1, 5.9 Hz, 2H), 3.72 (tt, J=8.5, 5.9 Hz, 1H), 2.43-2.07 (m, 3H), 1.92-1.39 (m, 8H), 1.23-1.17 (m, 9H); MS (ESI(+)) m/e 448 (M+H)⁺.

Example 845 N-(4-{8-[(1-methylcyclopropyl)carbonyl]-8-azabicyclo[3.2.1]oct-3-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(4-(8-azabicyclo[3.2.1]octan-3-yl)phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 1-methylcyclopropylacetic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.03 (s, 1H), 8.56 (dd, J=4.5, 1.3 Hz, 1H), 7.56-7.49 (m, 2H), 7.38 (dd, J=8.9, 4.5 Hz, 1H), 7.26-7.15 (m, 2H), 6.82 (dd, J=8.9, 1.4 Hz, 1H), 4.62-4.38 (m, 2H), 4.23 (t, J=8.3 Hz, 2H), 4.14 (dd, J=8.1, 5.9 Hz, 2H), 3.72 (tt, J=8.5, 5.9 Hz, 1H), 2.37-2.21 (m, 1H), 1.93-1.45 (m, 8H), 1.28 (d, J=5.7 Hz, 3H), 1.02-0.72 (m, 2H), 0.51 (dd, J=6.2, 2.1 Hz, 2H); MS (ESI(+)) m/e 446 (M+H)⁺.

Example 846 N-{4-[1-(2-methoxyethyl)-3-(2-methylpropyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 805, substituting 4-methylpent-1-yne for ethynylcyclopropane in Example 805A and (2-methoxyethyl)hydrazine for methylhydrazine in 805B. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.21 (s, 1H), 8.56 (dd, J=4.4, 1.2 Hz, 1H), 7.78-7.58 (m, 4H), 7.24 (d, J=8.5 Hz, 1H), 6.42 (s, 1H), 4.45-4.25 (m, 3H), 4.18 (t, J=5.5 Hz, 2H), 3.87-3.73 (m, 1H), 3.69 (t, J=5.5 Hz, 2H), 3.46-3.30 (m, 4H), 3.22 (s, 3H), 2.01-1.84 (m, 1H), 0.95 (d, J=6.6 Hz, 6H); MS (ESI(+)) m/e 435 (M+H)⁺.

Example 853 benzyl 4-[4-({[1-(6-chloropyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-4-fluoropiperidine-1-carboxylate

The title compound was prepared as described in Example 809C, substituting benzyl 4-[4-({[1-(6-chloropyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-4-hydroxypiperidine-1-carboxylate for tert-butyl 4-(4-(1-((benzyloxy)carbonyl)azetidine-3-carboxamido)phenyl)-4-hydroxypiperidine-1-carboxylate. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.18-10.11 (m, 1H), 7.67-7.57 (m, 2H), 7.53 (d, J=9.3 Hz, 1H), 7.47-7.23 (m, 7H), 6.96 (d, J=9.3 Hz, 1H), 5.14-5.08 (m, 2H), 4.26 (t, J=8.4 Hz, 2H), 4.17 (dd, J=8.3, 5.8 Hz, 2H), 4.09-3.98 (m, 2H). 3.80-3.60 (m, 2H), 3.30-3.20 (m, 2H), 2.2-1.8 (m, 3H); MS (ESI(+)) m/e 524 (M+H)⁺.

Example 854 benzyl 4-[4-({[1-(6-chloropyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-4-hydroxypiperidine-1-carboxylate Example 854A benzyl 4-(4-aminophenyl)-4-hydroxypiperidine-1-carboxylate

The title compound was prepared as described in Example 809A, substituting benzyl 4-oxopiperidine-1-carboxylate for tert-butyl 4-oxopiperidine-1-carboxylate.

Example 854B benzyl 4-[4-({[1-(6-chloropyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-4-hydroxypiperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting benzyl 4-(4-aminophenyl)-4-hydroxypiperidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 1-(6-chloropyridazin-3-yl)azetidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.06 (s, 1H), 7.59-7.49 (m, 3H), 7.41-7.28 (m, 7H), 6.96 (d, J=9.3 Hz, 1H), 5.09 (s, 2H), 5.04 (s, 1H), 4.26 (t, J=8.4 Hz, 2H), 4.16 (dd, J=8.3, 5.8 Hz, 2H), 3.97-3.86 (m, 2H), 3.73 (tt, J=8.5, 5.8 Hz, 1H), 3.3-3.0 (m, 2H), 1.91-1.70 (m, 2H), 1.63-1.54 (m, 2H); MS (ESI(+)) m/e 522.0 (M+H)⁺.

Example 857 N-{4-[4-fluoro-1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide Example 857A N-(4-(4-fluoropiperidin-4-yl)phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting tert-butyl 4-fluoro-4-[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 857B N-{4-[4-fluoro-1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(4-(4-fluoropiperidin-4-yl)phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2-fluorobenzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 10.06 (s, 1H), 7.59-7.49 (m, 3H), 7.41-7.28 (m, 7H), 6.96 (d, J=9.3 Hz, 1H), 5.09 (s, 2H), 5.04 (s, 1H), 4.26 (t, J=8.4 Hz, 2H), 4.16 (dd, J=8.3, 5.8 Hz, 2H), 3.97-3.86 (m, 2H), 3.73 (tt, J=8.5, 5.8 Hz, 1H), 3.3-3.0 (m, 2H), 1.91-1.70 (m, 2H), 1.63-1.54 (m, 2H); MS (ESI(+)) m/e 478 (M+H)⁺.

Example 863 N-[4-(1-benzoyl-4-fluoropiperidin-4-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(4-(4-fluoropiperidin-4-yl)phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and benzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.20-10.03 (m, 1H), 8.57 (d, J=4.5 Hz, 1H), 7.68-7.59 (m, 2H), 7.60-7.30 (m, 8H), 6.87-6.80 (m, 1H), 4.78-4.09 (m, 5H), 4.10-3.44 (m, 3H), 3.14-3.01 (m, 1H), 2.25-1.51 (m, 4H); MS (ESI(+)) m/e 460 (M+H)⁺.

Example 864 N-{4-[1-(2,2-dimethylpropanoyl)-4-fluoropiperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(4-(4-fluoropiperidin-4-yl)phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2,2-dimethypropanoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.20-10.02 (m, 1H), 8.56 (dd, J=4.5, 1.3 Hz, 1H), 7.67-7.58 (m, 2H), 7.47-7.30 (m, 3H), 6.83 (dd, J=8.9, 1.4 Hz, 1H), 4.48-4.10 (m, 6H), 3.80-3.69 (m, 1H), 3.23-2.96 (m, 2H), 2.07-1.60 (m, 4H), 1.23 (s, 9H); MS (ESI(+)) m/e 440 (M+H)⁺.

Example 865 N-{4-[3-tert-butyl-1-(2-methoxy ethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 805, substituting 3,3-dimethylbut-1-yne for ethynylcyclopropane in Example 805A and (2-methoxyethyl)hydrazine for methylhydrazine in Example 805B. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.14 (s, 1H), 8.57 (dd, J=4.5, 1.3 Hz, 1H), 7.70 (d, J=8.7 Hz, 2H), 7.64 (d, J=8.7 Hz, 2H), 7.39 (dd, J=8.9, 4.5 Hz, 1H), 6.84 (d, J=8.9 Hz, 1H), 6.40 (s, 1H), 4.31 (t, J=6.0 Hz, 2H), 4.25 (t, J=8.3 Hz, 2H), 4.17 (dd, J=8.0, 6.0 Hz, 2H), 3.83 (t, J=6.0 Hz, 2H), 3.75 (tt, J=8.7, 6.1 Hz, 1H), 3.25 (s, 3H), 1.37 (s, 9H); MS (ESI(+)) m/e 435 (M+H)⁺.

Example 866 N-[4-(1-butyl-3-tert-butyl-1H-pyrazol-5-yl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 805, substituting 3,3-dimethylbut-1-yne for ethynylcyclopropane in Example 805A and butylhydrazine for methylhydrazine in 805B. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.14 (s, 1H), 8.57 (dd, J=4.5, 1.3 Hz, 1H), 7.69 (d, J=8.7 Hz, 2H), 7.63 (d, J=8.8 Hz, 2H), 7.39 (dd, J=8.9, 4.5 Hz, 1H), 6.84 (dd, J=8.9, 1.3 Hz, 1H), 6.38 (s, 1H), 4.25 (t, J=8.3 Hz, 2H), 4.21-4.09 (m, 4H), 3.81-3.70 (m, 1H), 1.92-1.77 (m, 2H), 1.46-1.37 (m, 2H), 1.36 (s, 9H), 0.94 (t, J=7.3 Hz, 3H); MS (ESI(+)) m/e 433 (M+H)⁺.

Example 867 N-{4[3-tert-butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 805, substituting 3,3-dimethylbut-1-yne for ethynylcyclopropane in Example 805A and (tetrahydro-2H-pyran-4-ylmethyl)hydrazine for methylhydrazine in Example 805B. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.14 (s, 1H), 8.57 (dd, J=4.5, 1.3 Hz, 1H), 7.70 (d, J=8.7 Hz, 2H), 7.63 (d, J=8.8 Hz, 2H), 7.39 (dd, J=8.9, 4.5 Hz, 1H), 6.83 (dd, J=8.9, 1.4 Hz, 1H), 6.41 (s, 1H), 4.25 (t, J=8.3 Hz, 2H), 4.16 (dd, J=8.1, 5.9 Hz, 2H), 4.03 (d, J=7.0 Hz, 2H), 3.85 (dd, J=11.3, 3.0 Hz, 2H), 3.80-3.71 (m, 1H), 3.32-3.22 (m, 2H), 2.39-2.25 (m, 1H), 1.55 (dd, J=12.8, 1.9 Hz, 2H), 1.37 (s, 9H), 1.42-1.30 (m, 2H); MS (ESI(+)) m/e 475 (M+H)⁺.

Example 868 N-{2-fluoro-4[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide Example 868A tert-butyl 4-(4-(1-(5,6-dichloropyridazin-4-yl)azetidine-3-carboxamido)-3-fluorophenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 618, substituting tert-butyl 4-(4-(azetidine-3-carboxamido)-3-fluorophenyl)piperidine-1-carboxylate for (R)-5-(1-isobutyl-1H-pyrazol-4-yl)-N-(pyrrolidin-3-yl)thiophene-2-carboxamide.

Example 868B tert-butyl 4-(3-fluoro-4-(1-(pyridazin-4-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 147B, substituting tert-butyl 4-(4-(1-(5,6-dichloropyridazin-4-yl)azetidine-3-carboxamido)-3-fluorophenyl)piperidine-1-carboxylate for 4-(4-(1-(6-chloropyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate.

Example 868C N-(2-fluoro-4-(piperidin-4-yl)phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting tert-butyl 4-(3-fluoro-4-(1-(pyridazin-4-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 868D N-{2-fluoro-4[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(2-fluoro-4-(piperidin-4-yl)phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2-fluorobenzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.39 (s, 1H), 8.66 (d, J=6.3 Hz, 1H), 8.52 (d, J=3.0 Hz, 1H), 7.66-7.37 (m, 4H), 7.35-7.27 (m, 3H), 6.68 (dd, J=6.3, 3.2 Hz, 1H), 4.71-4.62 (m, 1H), 4.37-3.92 (m, 4H), 3.94-2.70 (m, 5H), 1.88-12 (m, 4H); MS (ESI(+)) m/e 478 (M+H)⁺.

Example 869 N-[4-(1-benzoylpiperidin-4-yl)-2-fluorophenyl]-1-(pyridazin-4-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(2-fluoro-4-(piperidin-4-yl)phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and benzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.27 (s, 1H), 8.61 (dd, J=6.0, 0.9 Hz, 1H), 8.51 (dd, J=3.0, 0.9 Hz, 1H), 7.57 (dd, J=12.9, 2.0 Hz, 1H), 7.51-7.38 (m, 5H), 7.34 (t, J=8.4 Hz, 1H), 7.28 (dd, J=8.4, 2.0 Hz, 1H), 6.55 (dd, J=6.0, 3.0 Hz, 1H), 4.71-4.51 (m, 1H), 4.22 (t, J=8.4 Hz, 2H), 4.12 (dd, J=8.2, 5.7 Hz, 2H), 4.04-3.45 (m, 2H), 3.22-2.76 (m, 3H), 2.08-1.33 (m, 4H); MS (ESI(+)) m/e 460 (M+H)⁺.

Example 870 N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(2-fluoro-4-(piperidin-4-yl)phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2,2-dimethylpropanoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (500 MHz, DMSO-d₆) δ ppm 10.28 (s, 1H), 8.61 (dd, J=6.0, 0.9 Hz, 1H), 8.51 (d, J=3.4 Hz, 1H), 7.68-7.24 (m, 3H), 6.57 (dd, J=6.1, 3.0 Hz, 1H), 4.5 (d, 2H), 4.30-4.13 (m, 4H), 3.90-2.78 (m, 4H), 1.79-1.71 (m, 2H), 1.72-1.44 (m, 2H), 1.21 (s, 9H); MS (ESI(+)) m/e 440 (M+H)⁺.

Example 871 N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-2-fluorophenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(2-fluoro-4-(piperidin-4-yl)phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 3,3,-dimethylbutanoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (500 MHz, DMSO-d₆) δ ppm 10.28 (s, 1H), 8.62 (d, J=6.1 Hz, 1H), 8.51 (d, J=3.4 Hz, 1H), 7.60-7.23 (m, 3H), 6.57 (dd, J=6.1, 3.0 Hz, 1H), 4.65-4.58 (m, 1H), 4.30-4.00 (m, 5H), 3.85-2.83 (m, 3H), 2.60-2.50 (m, 1H), 2.30 (d, J=14.0 Hz, 1H), 2.21 (d, J=14.0 Hz, 1H), 1.79-1.40 (m, 4H), 1.00 (s, 9H); MS (ESI(+)) m/e 454 (M+H)⁺.

Example 872 N-{2-fluoro-4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}-1-(pyridazin-4-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(2-fluoro-4-(piperidin-4-yl)phenyl)-1-(pyridazin-4-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 4,4,4-trifluorobutanoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (500 MHz, DMSO-d₆) δ ppm 10.3 (s, 1H), 8.70-8.50 (m, 2H), 7.90-7.20 (m, 3H), 6.55-6.65 (m, 1H), 4.6 (, d, 1H), 4.30-3.90 (m, 5H), 3.80-2.90 (m, 3H), 2.80-2.50 (m, 5H), 1.80-1.40 (m, 4H); MS (ESI(+)) m/e 480 (M+H)⁺.

Example 873 N-(4-{1-[(4-methylpiperidin-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described as described in Example 148A, substituting N-(4-bromophenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for 4-bromoaniline and tert-butyl 4-methyl-4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)methyl)piperidine-1-carboxylate for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole followed by TFA deprotection as described in Example 1D to give the title compound as a TFA salt. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.24 (s, 1H), 8.57 (d, J=4.0 Hz, 1H), 8.52 (s, 1H), 8.40 (s, 1H), 8.11 (s, 1H), 7.87 (s, 1H), 7.80 (dd, J=9.3, 4.3 Hz, 1H), 7.63 (d, J=8.6 Hz, 2H), 7.55 (d, J=8.5 Hz, 2H), 7.45 (d, J=9.3 Hz, 1H), 4.47 (t, J=9.1 Hz, 2H), 4.43-4.34 (m, 2H), 4.08 (s, 2H), 3.81 (ddd, J=14.5, 8.7, 6.0 Hz, 1H), 3.27-3.13 (m, 2H), 3.13-2.97 (m, 2H), 1.73-1.58 (m, 2H), 1.57-1.42 (m, 2H), 0.98 (s, 3H); MS (ESI(+)) m/e 432 (M+H)⁺.

Example 874 N-{4-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 805, substituting 3,3,3-trifluoroprop-1-yne for ethynylcyclopropane in Example 805A. ¹H NMR (500 MHz, DMSO-d₆) δ ppm 10.47 (s, 1H), 8.57 (d, J=3.8 Hz, 1H), 7.80 (d, J=8.4 Hz, 2H), 7.57 (d, J=8.4 Hz, 2H), 7.56-7.49 (m, 1H), 7.06 (d, J=8.6 Hz, 1H), 6.87 (s, 1H), 4.34 (t, J=8.4 Hz, 2H), 4.29-4.22 (m, 2H), 3.92 (s, 3H), 3.86-3.78 (m, 1H); MS (ESI(+)) m/e 403 (M+H)⁺.

Example 875 1-(6-chloropyridazin-3-yl)-N-{4-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]phenyl}azetidine-3-carboxamide Example 875A 4-(1-neopentyl-1H-pyrazol-4-yl)aniline

The title compound was prepared as described as described in Example 148A, substituting 1-neopentyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.

Example 875B 1-(6-chloropyridazin-3-yl)-N-{4-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]phenyl}azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting 4-(1-neopentyl-1H-pyrazol-4-yl)aniline for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 1-(6-chloropyridazin-3-yl)azetidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.10 (s, 1H), 8.04 (s, 1H), 7.82 (s, 1H), 7.61 (d, J=8.7 Hz, 2H), 7.56-7.50 (m, 3H), 6.98 (d, J=9.3 Hz, 1H), 4.27 (t, J=8.5 Hz, 2H), 4.19 (dd, J=8.3, 5.9 Hz, 2H), 3.90 (s, 2H), 3.74 (tt, J=8.6, 5.9 Hz, 1H), 0.92 (s, 9H); MS (ESI(+)) m/e 425 (M+H)⁺.

Example 876 N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-methylpyridin-3-yl)azetidine-3-carboxamide Example 876A tert-butyl 4-(4-(1-(6-methylpyridin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1C, substituting 5-bromo-2-methylpyridine for 3-bromopyridine and tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 876B 1-(6-methylpyridin-3-yl)-N-(4-(piperidin-4-yl)phenyl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting tert-butyl 4-(4-(1-(6-methylpyridin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 876C N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-methylpyridin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting 1-(6-methylpyridin-3-yl)-N-(4-(piperidin-4-yl)phenyl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and benzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 9.99 (s, 1H), 7.73 (d, J=2.8 Hz, 1H), 7.53 (d, J=8.5 Hz, 2H), 7.48-7.39 (m, 5H), 7.22 (d, J=8.6 Hz, 2H), 7.04 (d, J=8.3 Hz, 1H), 6.80 (dd, J=8.3, 2.9 Hz, 1H), 4.62 (s, 1H), 4.05 (t, J=7.7 Hz, 2H), 3.90 (t, J=6.7 Hz, 2H), 3.69 (ddd, J=14.5, 8.1, 6.3 Hz, 2H), 3.13 (s, 1H), 2.99-2.69 (m, 2H), 2.34 (s, 3H), 1.89-1.47 (m, 4H), MS (ESI(+)) m/e 455 (M+H)⁺.

Example 877 N-(4-{1-[(4-methylpiperidin-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide Example 877A tert-butyl 1-(pyridin-3-yl)azetidine-3-carboxylate

The title compound was prepared as described in Example 1C, substituting tert-butyl azetidine-3-carboxylate for tert-butyl 4-(4-(azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 877B 1-(pyridin-3-yl)azetidine-3-carboxylic acid

The title compound was prepared as described in Example 1D, substituting tert-butyl 1-(pyridin-3-yl)azetidine-3-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 877C N-(4-bromophenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting 4-bromoaniline for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 1-(pyridin-3-yl)azetidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 877D N-(4-{1-[(4-methylpiperidin-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide

The title compound as described as described in Example 148A, substituting N-(4-bromophenyl)-1-(pyridin-3-yl)azetidine-3-carboxamide for 4-bromoaniline and tert-butyl 4-methyl-4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)methyl)piperidine-1-carboxylate for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole followed by TFA deprotection as described in Example 1D to give the title compound as a TFA salt. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.21 (s, 1H), 8.58 (s, 1H), 8.45 (s, 1H), 8.15 (d, J=5.3 Hz, 1H), 8.10 (s, 1H), 8.08 (d, J=2.6 Hz, 1H), 7.86 (s, 1H), 7.77 (dd, J=8.6, 5.4 Hz, 1H), 7.62 (d, J=8.7 Hz, 2H), 7.58-7.51 (m, 3H), 4.24 (t, J=8.3 Hz, 2H), 4.15 (dd, J=7.9, 6.0 Hz, 2H), 4.08 (s, 2H), 3.79 (dq, J=8.6, 5.9 Hz, 1H), 3.28-3.12 (m, 2H), 3.12-2.95 (m, 2H), 1.65 (ddd, J=13.4, 9.3, 3.8 Hz, 2H), 1.56-1.40 (m, 2H), 0.97 (s, 3H); MS (ESI(+)) m/e 431 (M+H)⁺.

Example 878 N-{4-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide

To 1-(6-chloropyridazin-3-yl)-N-(4-(1-neopentyl-1H-pyrazol-4-yl)phenyl)azetidine-3-carboxamide (0.076 g, 0.179 mmol) was added methylzinc(II) chloride (2.0M in THF) (0.179 ml, 0.358 mmol) and 5 mg of palladium catalyst. The reaction mixture was heated to 60° C. and a thick precipitate developed. N-methylpyrrolidine (0.2 ml) was added and the mixture was heated to 85° C. for 2 hours. The mixture was diluted with dichloromethane and purified by normal phase chromatography to give the title compound. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.11 (s, 1H), 8.04 (s, 1H), 7.82 (s, 1H), 7.61 (d, J=8.7 Hz, 2H), 7.53 (d, J=8.7 Hz, 2H), 7.43 (d, J=9.2 Hz, 1H), 6.99 (d, J=9.1 Hz, 1H), 4.27 (t, J=8.5 Hz, 2H), 4.19 (dd, J=8.2, 6.1 Hz, 2H), 3.90 (s, 2H), 3.75 (ddd, J=17.0, 8.5, 6.0 Hz, 1H), 2.45 (s, 3H), 0.92 (s, 9H); MS (ESI(+)) m/e 405 (M+H)⁺.

Example 879 N-{3-fluoro-4[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide Example 879A tert-butyl 4-(4-amino-2-fluorophenyl)-5,6-dihydropyridine-1(2H)-carboxylate

The title compound was prepared as described as described in Example 148A, substituting 4-bromo-3-fluoroaniline for 4-bromoaniline and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.

Example 879B tert-butyl 4-(4-amino-2-fluorophenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1B, substituting tert-butyl 4-(4-amino-2-fluorophenyl)-5,6-dihydropyridine-1(2H)-carboxylate for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 879C tert-butyl 4-(2-fluoro-4-(1-(pyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting tert-butyl 4-(4-amino-2-fluorophenyl)piperidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 1-(pyridazin-3-yl)azetidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 879D N-(3-fluoro-4-(piperidin-4-yl)phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting tert-butyl 4-(2-fluoro-4-(1-(pyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 879E N-{3-fluoro-4[1-(3-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(3-fluoro-4-(piperidin-4-yl)phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 3-fluorobenzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 9.86 (s, 1H), 8.56 (dd, J=4.5, 1.1 Hz, 1H), 7.79 (t, J=8.3 Hz, 1H), 7.56-7.45 (m, 1H), 7.38 (dd, J=9.0, 4.5 Hz, 1H), 7.25 (ddd, J=20.2, 14.3, 8.7 Hz, 4H), 7.10 (d, J=8.2 Hz, 1H), 6.83 (dd, J=8.9, 1.0 Hz, 1H), 4.60 (s, 1H), 4.19 (dt, J=14.0, 8.2 Hz, 4H), 3.99-3.74 (m, 1H), 3.59 (s, 1H), 3.07 (d, J=59.7 Hz, 1H), 2.85 (dd, J=39.3, 27.7 Hz, 2H), 2.08-1.43 (m, 4H); MS (ESI(+)) m/e 478.3 (M+H)⁺.

The following Examples were essentially prepared as described in Example 879, substituting an appropriate carboxylic acid in Example 879E.

TABLE 21 Ex Name MS 880 N-{3-fluoro-4-[1-(2-methylpropanoyl)piperidin-4-yl] (ESI(+)) phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 426 (M + H)⁺ 881 N-{3-fluoro-4-[1-(3,3,3-trifluoropropanoyl)piperidin- (ESI(+)) 4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3- m/e 466 carboxamide (M + H)⁺ 882 N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-3- (ESI(+)) fluorophenyl}-1-(pyridazin-3-yl)azetidine-3- m/e 454 carboxamide (M + H)⁺ 883 N-{3-fluoro-4-[1-(4,4,4-trifluorobutanoyl)piperidin- (ESI(+)) 4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3- m/e 480 carboxamide (M + H)⁺ 884 N-[4-(1-benzoylpiperidin-4-yl)-3-fluorophenyl]-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 460 (M + H)⁺ 885 N-{3-fluoro-4-[1-(2-fluorobenzoyl)piperidin-4-yl] (ESI(+)) phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 478 (M + H)⁺ 886 N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]-3- (ESI(+)) fluorophenyl}-1-(pyridazin-3-yl)azetidine-3- m/e 440 carboxamide (M + H)⁺ 887 N-{3-fluoro-4-[1-(3-methylbutanoyl)piperidin-4-yl] (ESI(+)) phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 440 (M + H)⁺ 888 N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]-3- (ESI(+)) fluorophenyl}-1-(pyridazin-3-yl)azetidine-3- m/e 438 carboxamide (M + H)⁺

Example 889 N-{4-[1-(2-fluorobenzoyl)-4-hydroxypiperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide Example 889A benzyl 4-(4-(1-(6-chloropyridazin-3-yl)azetidine-3-carboxamido)phenyl)-4-hydroxypiperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting benzyl 4-(4-aminophenyl)-4-hydroxypiperidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 1-(6-chloropyridazin-3-yl)azetidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 889B N-(4-(4-hydroxypiperidin-4-yl)phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1B, substituting benzyl 4-(4-(1-(6-chloropyridazin-3-yl)azetidine-3-carboxamido)phenyl)-4-hydroxypiperidine-1-carboxylate for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 889C N-{4-[1-(2-fluorobenzoyl)-4-hydroxypiperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(4-(4-hydroxypiperidin-4-yl)phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2-fluorobenzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.08 (s, 1H), 8.56 (dd, J=4.5, 1.3 Hz, 1H), 7.61-7.54 (m, 2H), 7.55-7.33 (m, 5H), 7.35-7.22 (m, 2H), 6.83 (dd, J=8.9, 1.3 Hz, 1H), 5.16 (s, 1H), 4.50-4.42 (m, 1H), 4.24 (t, J=8.3 Hz, 2H), 4.15 (dd, J=8.1, 5.9 Hz, 2H), 3.79-3.68 (m, 1H), 3.52-3.41 (m, 1H), 3.27-3.13 (m, 2H), 2.07-1.65 (m, 3H), 1.66-1.40 (m, 1H); MS (ESI(+)) m/e 476.1 (M+H)⁺.

Example 890 N-{4-[1-(2,2-dimethylpropanoyl)-4-hydroxypiperidin-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(4-(4-hydroxypiperidin-4-yl)phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2,2-dimethylpropanoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.06 (s, 1H), 8.56 (dd, J=4.5, 1.3 Hz, 1H), 7.59-7.53 (m, 2H), 7.46-7.33 (m, 3H), 6.83 (dd, J=8.9, 1.3 Hz, 1H), 5.06 (s, 1H), 4.30-4.08 (m, 6H), 3.79-3.68 (m, 1H), 3.25-3.13 (m, 2H), 1.83-1.68 (m, 2H), 1.66-1.58 (m, 2H), 1.22 (s, 9H); MS (ESI(+)) m/e 438.2 (M+H)⁺.

Example 891 1-(6-methylpyridazin-3-yl)-N-(4-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)azetidine-3-carboxamide Example 891A tert-butyl 1-(6-methylpyridazin-3-yl)azetidine-3-carboxylate

The title compound was prepared as described in Example 1C, substituting 3-chloro-6-methylpyridazine for 3-bromopyridine and tert-butyl azetidine-3-carboxylate for tert-butyl 4-(4-(azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 891B 1-(6-methylpyridazin-3-yl)azetidine-3-carboxylic acid

The title compound was prepared as described in Example 1D, substituting tert-butyl 1-(6-methylpyridazin-3-yl)azetidine-3-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 891C N-(4-bromophenyl)-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting 4-bromoaniline for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 1-(6-methylpyridazin-3-yl)azetidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 891D 1-(6-methylpyridazin-3-yl)-N-(4-{1-[(4-methyltetrahydro-2H-pyran-4-yl)methyl]-1H-pyrazol-4-yl}phenyl)azetidine-3-carboxamide

The title compound was prepared as described as described in Example 148A, substituting N-(4-bromophenyl)-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide for 4-bromoaniline and 1-((4-methyltetrahydro-2H-pyran-4-yl)methyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.08 (s, 1H), 8.06 (s, 1H), 7.82 (s, 1H), 7.61 (d, J=8.7 Hz, 2H), 7.52 (d, J=8.6 Hz, 2H), 7.29 (d, J=9.1 Hz, 1H), 6.79 (d, J=9.0 Hz, 1H), 4.20 (t, J=8.2 Hz, 2H), 4.12 (dd, J=7.8, 6.2 Hz, 2H), 4.02 (s, 2H), 3.78-3.64 (m, 3H), 3.52 (ddd, J=11.8, 9.3, 2.9 Hz, 2H), 2.44 (s, 3H), 1.51 (ddd, J=13.3, 9.1, 4.1 Hz, 2H), 1.30-1.19 (m, 2H), 0.97 (s, 3H); MS (ESI(+)) m/e 447 (M+H)⁺.

Example 892 (3S)—N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide Example 892A

(S)-tert-butyl 4-(4-(1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1C, substituting 3-bromo-6-methylpyridazine for 3-bromopyridine and (S)-tert-butyl 4-(4-(pyrrolidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 892B (S)-1-(6-methylpyridazin-3-yl)-N-(4-(piperidin-4-yl)phenyl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting (S)-tert-butyl 4-(4-(1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

The title compound was prepared as described in Example 1A, substituting (S)-1-(6-methylpyridazin-3-yl)-N-(4-(piperidin-4-yl)phenyl)pyrrolidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2-fluorobenzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.25-9.59 (m, 1H), 7.63-7.39 (m, 4H), 7.38-7.11 (m, 5H), 6.84 (dd, J=10.8, 7.3 Hz, 1H), 4.79-4.47 (m, 1H), 3.85-3.39 (m, 6H), 3.25-3.07 (m, 1H), 3.00-2.68 (m, 2H), 2.42 (s, 3H), 2.37-2.09 (m, 2H), 1.97-1.37 (m, 4H); MS (ESI(+)) m/e 488.3 (M+H)⁺.

(S)-tert-butyl 4-(4-(pyrrolidine-3-carboxamido)phenyl)piperidine-1-carboxylate Example 893 (3S)—N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting (S)-1-(6-methylpyridazin-3-yl)-N-(4-(piperidin-4-yl)phenyl)pyrrolidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and benzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.25-9.84 (m, 1H), 7.62-7.51 (m, 2H), 7.50-7.36 (m, 5H), 7.31-7.12 (m, 3H), 6.91-6.76 (m, 1H), 4.77-4.30 (m, 1H), 3.98-3.37 (m, 7H), 3.02-2.62 (m, 2H), 2.42 (s, 3H), 2.38-2.01 (m, 2H), 1.97-1.43 (m, 4H); MS (ESI(+)) m/e 470.2 (M+H)⁺.

Example 894 (3S)—N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(6-methylpyridazin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting (S)-1-(6-methylpyridazin-3-yl)-N-(4-(piperidin-4-yl)phenyl)pyrrolidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2,2-dimethylpropanoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.04 (s, 1H), 7.56-7.50 (m, 2H), 7.23 (d, J=9.1 Hz, 1H), 7.21-7.14 (m, 2H), 6.83 (d, J=9.1 Hz, 1H), 4.45-4.36 (m, 2H), 3.74 (dd, J=10.3, 7.9 Hz, 1H), 3.64-3.52 (m, 2H), 3.50-3.39 (m, 1H), 3.35-3.25 (m, 1H), 2.93-2.66 (m, 3H), 2.40 (s, 3H), 2.37-2.11 (m, 2H), 1.82-1.74 (m, 2H), 1.53-1.35 (m, 2H), 1.22 (s, 9H); MS (ESI(+)) m/e 450.3 (M+H)⁺.

Example 895 N-{4[(1-benzoylpiperidin-4-yl)methyl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide Example 895A 4-(pyridin-4-ylmethyl)aniline

The title compound was prepared as described in Example 1B, substituting 4-(4-nitrobenzyl)pyridine for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 348B 2,2,2-trifluoro-N-(4-(pyridin-4-ylmethyl)phenyl)acetamide

A solution of 4-(pyridin-4-ylmethyl)aniline (21.6 g, 117 mmol) and triethylamine (19.61 ml, 141 mmol) in dichloromethane (586 ml) was cooled to 0° C. Trifluoroacetic anhydride (19.87 ml, 141 mmol) was added dropwise via additional funnel over a period of 20 minutes. The mixture was stirred at 0° C. for 1 hour and then at room temperature for 2 hours. The reaction mixture was then concentrated in vacuo and the resulting residue was purified by regular phase column chromatography to give the title compound.

Example 895C 2,2,2-trifluoro-N-(4-(piperidin-4-ylmethyl)phenyl)acetamide

2,2,2-Trifluoro-N-(4-(pyridin-4-ylmethyl)phenyl)acetamide (28.5 g, 102 mmol) and acetic acid (205 ml) were added to platinum(IV) oxide (3.42 g, 15.06 mmol) in a 500 mL stainless steel pressure bottle and the mixture was stirred for 16 hours at 40 psi. The mixture was filtered through a nylon membrane and concentrated in vacuo; and the resulting residue was taken up in methanol (100 mL) and poured into diethyl ether (600 mL). The precipitate was filtered, washed with ether and dried with sodium sulfate to afford the title compound.

Example 895D tert-butyl 4-(4-aminobenzyl)piperidine-1-carboxylate

A solution of 2,2,2-trifluoro-N-(4-(piperidin-4-ylmethyl)phenyl)acetamide (26.4 g, 92 mmol) in dichloromethane (369 ml) was cooled to 0° C. and triethylamine (19.28 ml, 138 mmol) was added slowly. To the resulting solution was added di-tert-butyl dicarbonate (22.14 g, 101 mmol) in dichloromethane (75 ml) via addition funnel over 10 minutes. The 0° C. mixture was stirred for 2 hours and warmed slowly overnight. The reaction mixture was recooled to 0° C., treated with 1 N aqueous sodium hydroxide (100 ml), warmed to room temperature and stirred for 1 hour. The bilayer was separated and the organics were washed with water and brine, dried with magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by normal phase chromatography to give the title compound.

Example 895E tert-butyl 4-(4-(1-(pyridazin-3-yl)azetidine-3-carboxamido)benzyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting tert-butyl 4-(4-aminobenzyl)piperidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 1-(pyridazin-3-yl)azetidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 895F N-(4-(piperidin-4-ylmethyl)phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting tert-butyl 4-(4-(1-(pyridazin-3-yl)azetidine-3-carboxamido)benzyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 895G

The title compound was prepared as described in Example 1A, substituting N-(4-(piperidin-4-ylmethyl)phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and benzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.03 (s, 1H), 8.56 (dd, J=4.5, 1.3 Hz, 1H), 7.52 (d, J=8.5 Hz, 2H), 7.47-7.28 (m, 6H), 7.11 (d, J=8.5 Hz, 2H), 6.83 (dd, J=9.0, 1.3 Hz, 1H), 4.58-4.34 (m, 1H), 4.23 (t, J=8.3 Hz, 2H), 4.14 (dd, J=8.1, 6.0 Hz, 2H), 3.72 (tt, J=8.6, 6.0 Hz, 1H), 3.66-3.47 (m, 1H), 3.08-2.83 (m, 1H), 2.83-2.59 (m, 1H), 1.87-1.69 (m, 1H), 1.69-1.57 (m, 1H), 1.57-1.41 (m, 1H), 1.31-0.90 (m, 2H); MS (ESI(+)) m/e 456 (M+H)⁺.

The following Examples were essentially prepared as described in Example 895, substituting an appropriate carboxylic acid in Example 895G. Some products were purified by flash chromatography while others were purified by reverse-phase HPLC. Accordingly, some Examples were isolated as trifluoroacetic acid salts.

TABLE 22 Ex Name MS 896 N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]methyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3- m/e 474 carboxamide (M + H)⁺ 897 N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]methyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 436 (M + H)⁺ 898 N-(4-{[1-(3,3-dimethylbutanoyl)piperidin-4-yl]methyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 450 (M + H)⁺ 899 N-(4-{[1-(2-ethylbutanoyl)piperidin-4-yl]methyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 450 (M + H)⁺ 900 1-(pyridazin-3-yl)-N-(4-{[1-(4,4,4-trifluorobutanoyl) (ESI(+)) piperidin-4-yl]methyl}phenyl)azetidine-3- m/e 476 carboxamide (M + H)⁺ 901 N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]methyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 422 (M + H)⁺ 902 N-{4-[(1-acetylpiperidin-4-yl)methyl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 394 (M + H)⁺ 903 N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}methyl) (ESI(+)) phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 436 (M + H)⁺ 904 N-[4-({1-[(1-methylcyclopropyl)carbonyl]piperidin-4- (ESI(+)) yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3- m/e 434 carboxamide (M + H)⁺ 927 1-(pyridazin-3-yl)-N-(4-{[1-(1,3-thiazol-5-ylcarbonyl) (ESI(+)) piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide m/e 463 (M + H)⁺ 928 N-(4-{[1-(cyclopentylcarbonyl)piperidin-4-yl]methyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 448 (M + H)⁺ 929 N-(4-{[1-(1H-pyrazol-4-ylcarbonyl)piperidin-4-yl] (ESI(+)) methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3- m/e 446 carboxamide (M + H)⁺ 930 N-(4-{[1-(2,2-dimethylbutanoyl)piperidin-4-yl]methyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 450 (M + H)⁺ 931 N-[4-({1-[(2-methylcyclopropyl)carbonyl]piperidin-4- (ESI(+)) yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3- m/e 434 carboxamide (M + H)⁺ 932 N-[4-({1-[(methylsulfanyl)acetyl]piperidin-4-yl}methyl) (ESI(+)) phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 440 (M + H)⁺ 933 N-[4-({1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl] (ESI(+)) piperidin-4-yl}methyl)phenyl]-1-(pyridazin-3-yl) m/e 488 azetidine-3-carboxamide (M + H)⁺ 934 N-(4-{[1-(2-methylpentanoyl)piperidin-4-yl]methyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 450 (M + H)⁺ 935 N-(4-{[1-(4-methylpentanoyl)piperidin-4-yl]methyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 450 (M + H)⁺ 936 N-[4-({1-[3-(methylsulfanyl)propanoyl]piperidin-4- (ESI(+)) yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3- m/e 454 carboxamide (M + H)⁺ 937 1-(pyridazin-3-yl)-N-(4-{[1-(1,3-thiazol-4-ylcarbonyl) (ESI(+)) piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide m/e 463 (M + H)⁺ 938 N-(4-{[1-(1H-pyrazol-5-ylcarbonyl)piperidin-4-yl] (ESI(+)) methyl}phenyl)-1-(pyridazin-3-yl)azetidine-3- m/e 446 carboxamide (M + H)⁺ 939 N-[4-({1-[(6-methylpyridin-3-yl)carbonyl]piperidin-4- (ESI(+)) yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3- m/e 471 carboxamide (M + H)⁺ 940 N-[4-({1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4- (ESI(+)) yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3- m/e 476 carboxamide (M + H)⁺ 941 N-(4-{[1-(pent-4-ynoyl)piperidin-4-yl]methyl}phenyl)-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 432 (M + H)⁺ 942 1-(pyridazin-3-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl) (ESI(+)) piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide m/e 462 (M + H)⁺ 943 N-(4-{[1-(methoxyacetyl)piperidin-4-yl]methyl}phenyl)-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e XXX (M + H)⁺ 944 1-(pyridazin-3-yl)-N-(4-{[1-(tetrahydrofuran-2-ylcarbonyl) (ESI(+)) piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide m/e 424 (M + H)⁺ 945 N-[4-({1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}methyl) (ESI(+)) phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 468 (M + H)⁺ 946 N-(4-{[1-(ethoxyacetyl)piperidin-4-yl]methyl}phenyl)-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 438 (M + H)⁺ 947 1-(pyridazin-3-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl) (ESI(+)) piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide m/e 462 (M + H)⁺ 948 N-{4-[(1-hexanoylpiperidin-4-yl)methyl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 450 (M + H)⁺ 949 N-[4-({1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4- (ESI(+)) yl}methyl)phenyl]-1-(pyridazin-3-yl)azetidine-3- m/e 459 carboxamide (M + H)⁺ 950 N-(4-{[1-(but-3-enoyl)piperidin-4-yl]methyl}phenyl)-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 420 (M + H)⁺ 951 1-(pyridazin-3-yl)-N-(4-{[1-(1,3-thiazol-2-ylcarbonyl) (ESI(+)) piperidin-4-yl]methyl}phenyl)azetidine-3-carboxamide m/e 463 (M + H)⁺ 952 N-(4-{[1-(furan-2-ylcarbonyl)piperidin-4-yl]methyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 446 (M + H)⁺ 953 N-(4-{[1-(1,2-oxazol-5-ylcarbonyl)piperidin-4-yl]methyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 447 (M + H)⁺ 954 1-(pyridazin-3-yl)-N-(4-{[1-(pyridin-2-ylcarbonyl) (ESI(+)) piperidin-4-yl]methyl}phenyl)azetidine-3- m/e 457 carboxamide (M + H)⁺ 955 N-(4-{[1-(furan-3-ylcarbonyl)piperidin-4-yl]methyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 446 (M + H)⁺ 956 N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]methyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 434 (M + H)⁺ 957 N-(4-{[1-(2-methylbutanoyl)piperidin-4-yl]methyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 436 (M + H)⁺ 958 N-{4-[(1-propanoylpiperidin-4-yl)methyl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 408 (M + H)⁺ 959 N-{4-[(1-butanoylpiperidin-4-yl)methyl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 422 (M + H)⁺ 960 N-(4-{[1-(cyclobutylcarbonyl)piperidin-4-yl]methyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 434 (M + H)⁺ 961 N-{4-[(1-pentanoylpiperidin-4-yl)methyl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 436 (M + H)⁺ 962 N-(4-{[1-(cyclopentylacetyl)piperidin-4-yl]methyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 462 (M + H)⁺ 963 N-(4-{[1-(2-methylbenzoyl)piperidin-4-yl]methyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 470 (M + H)⁺ 964 N-(4-{[1-(3-methylpentanoyl)piperidin-4-yl]methyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 450 (M + H)⁺ 965 N-(4-{[1-(cyclohexylcarbonyl)piperidin-4-yl]methyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 462 (M + H)⁺ 966 N-(4-{[1-(3-methylbutanoyl)piperidin-4-yl]methyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 436 (M + H)⁺ 967 N-(4-{[1-(cyclopropylcarbonyl)piperidin-4-yl]methyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 420 (M + H)⁺ 968 1-(pyridazin-3-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl) (ESI(+)) piperidin-4- yl]methyl}phenyl)azetidine-3-carboxamide m/e 462 (M + H)⁺

Example 905 N-[4-(1-{[4-methyl-1-(oxetan-3-yl)piperidin-4-yl]methyl}-1H-pyrazol-4-yl)phenyl]-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide Example 905A tert-butyl 4-methyl-4-((4-(4-(1-(6-methylpyridazin-3-yl)azetidine-3-carboxamido)phenyl)-1H-pyrazol-1-yl)methyl)piperidine-1-carboxylate

The title compound was prepared as described as described in Example 148A, substituting N-(4-bromophenyl)-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide for 4-bromoaniline and tert-butyl 4-methyl-4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)methyl)piperidine-1-carboxylate for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.

Example 905B N-(4-(1((4-methylpiperidin-4-yl)methyl)-1H-pyrazol-4-yBphenyl)-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting tert-butyl 4-methyl-4-((4-(4-(1-(6-methylpyridazin-3-yl)azetidine-3-carboxamido)phenyl)-1H-pyrazol-1-yl)methyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 905C N-[4-(1-{[4-methyl-1-(oxetan-3-yl)piperidin-4-yl]methyl}-1H-pyrazol-4-yl)phenyl]-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide

N-(4-(1-((4-Methylpiperidin-4-yl)methyl)-1H-pyrazol-4-yl)phenyl)-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide was dissolved in methanol (3 ml) and treated with oxetan-3-one (0.022 ml, 0.338 mmol) and sodium cyanoborohydride (0.021 g, 0.338 mmol) and stiffed overnight. The mixture was concentrated, purified by normal phase chromatography, triturated with ether and concentrated to give the title compound. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.09 (s, 1H), 8.05 (s, 1H), 7.82 (s, 1H), 7.64-7.58 (m, 2H), 7.56-7.49 (m, 2H), 7.29 (d, J=9.1 Hz, 1H), 6.80 (d, J=9.0 Hz, 1H), 4.51 (t, J=6.4 Hz, 2H), 4.40 (t, J=5.8 Hz, 2H), 4.20 (t, J=8.3 Hz, 2H), 4.12 (dd, J=7.9, 6.1 Hz, 2H), 3.98 (s, 2H), 3.73 (tt, J=8.5, 6.1 Hz, 1H), 3.48-3.39 (m, 1H), 2.44 (s, 3H), 2.42-2.33 (m, 2H), 2.16-1.99 (m, 2H), 1.58-1.46 (m, 2H), 1.30 (d, J=12.6 Hz, 2H), 0.89 (s, 3H); MS (ESI(+)) m/e 502 (M+H)⁺.

Example 906 N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(4-methylpyridazin-3-yl)azetidine-3-carboxamide Example 906A tert-butyl 4-(4-(1-(4-methylpyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1C, substituting 3-chloro-4-methylpyridazine for 3-bromopyridine and tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 906B 1-(4-methylpyridazin-3-yl)-N-(4-(piperidin-4-yl)phenyl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting tert-butyl 4-(4-(1-(4-methylpyridazin-3-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 906C N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(4-methylpyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting 1-(4-methylpyridazin-3-yl)-N-(4-(piperidin-4-yl)phenyl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and benzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.03 (s, 1H), 8.49 (d, J=4.6 Hz, 1H), 7.58-7.52 (m, 2H), 7.53-7.37 (m, 5H), 7.25-7.17 (m, 3H), 4.81-4.37 (m, 1H), 4.39-4.25 (m, 4H), 4.26-3.38 (m, 2H), 3.24-2.58 (m, 3H), 2.19 (s, 3H), 2.10-1.11 (m, 4H); MS (ESI(+)) m/e 456.2 (M+H)⁺

Example 907 5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]furan-2-carboxamide Example 907A 5-(1-(tert-butoxycarbonyl)-1,2,3,6-tetrahydropyridin-4-yl)furan-2-carboxylic acid

The title compound was prepared as described as described in Example 148A, substituting 5-bromofuran-2-carboxylic acid for 4-bromoaniline and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.

Example 907B 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)furan-2-carboxylic acid

The title compound was prepared as described in Example 1B, substituting 5-(1-(tert-butoxycarbonyl)-1,2,3,6-tetrahydropyridin-4-yl)furan-2-carboxylic acid for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 907C (S)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-amine

The title compound was prepared as described in Example 1C, substituting 3,6-dichloropyridazine for 3-bromopyridine and (S)-tert-butyl pyrrolidin-3-ylcarbamate for tert-butyl 4-(4-(azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate followed by TFA deprotection as described in Example 1D.

Example 907D (S)-tert-butyl 4-(5-((1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl)carbamoyl)furan-2-yl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting (S)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-amine for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)furan-2-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 907E (S)-tert-butyl 4-(5-((1-(pyridazin-3-yl)pyrrolidin-3-yl)carbamoyl)furan-2-yl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1B, substituting (S)-tert-butyl 4-(5-((1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl)carbamoyl)furan-2-yl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 907F (S)-5-(piperidin-4-yl)-N-(1-(pyridazin-3-yl)pyrrolidin-3-yl)furan-2-carboxamide

The title compound was prepared as described in Example 1D, substituting (S)-tert-butyl 4-(5-((1-(pyridazin-3-yl)pyrrolidin-3-yl)carbamoyl)furan-2-yl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 907G 5-[1-(2-fluorobenzoyl)piperidin-4-yl]-N-[(3S)-1-(pyridazin-3-yl)pyrrolidin-3-yl]furan-2-carboxamide

The title compound was prepared as described in Example 1A, substituting (S)-5-(piperidin-4-yl)-N-(1-(pyridazin-3-yl)pyrrolidin-3-yl)furan-2-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2-fluorobenzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 8.48 (dd, J=4.4, 0.9 Hz, 1H), 8.40 (d, J=7.0 Hz, 1H), 7.55-7.46 (m, 1H), 7.41 (t, J=6.9 Hz, 1H), 7.37-7.24 (m, 3H), 7.06 (d, J=3.4 Hz, 1H), 6.86 (dd, J=9.1, 0.8 Hz, 1H), 6.31 (d, J=3.4 Hz, 1H), 4.67-4.47 (m, 2H), 3.76 (dd, J=10.8, 6.9 Hz, 1H), 3.70-3.59 (m, 1H), 3.59-3.48 (m, 1H), 3.48-3.39 (m, 2H), 3.19 (t, J=12.1 Hz, 1H), 3.08-2.89 (m, 2H), 2.33-2.19 (m, 1H), 2.13-2.02 (m, 2H), 1.99-1.88 (m, 1H), 1.67-1.41 (m, 2H); MS (ESI(+)) m/e 464 (M+H)⁺.

Example 908 N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(3-methylpyridazin-4-yl)azetidine-3-carboxamide Example 908A tert-butyl 4-(4-(1-(3-methylpyridazin-4-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1C, substituting 4-chloro-3-methylpyridazine for 3-bromopyridine and tert-butyl 4-(4-(azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 908B 1-(3-methylpyridazin-4-yl)-N-(4-(piperidin-4-yl)phenyl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting tert-butyl 4-(4-(1-(3-methylpyridazin-4-yl)azetidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 908C N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(3-methylpyridazin-4-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting 1-(3-methylpyridazin-4-yl)-N-(4-(piperidin-4-yl)phenyl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and benzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.05 (s, 1H), 8.55 (d, J=5.8 Hz, 1H), 7.57-7.51 (m, 2H), 7.49-7.33 (m, 5H), 7.26-7.19 (m, 2H), 6.45 (d, J=5.8 Hz, 1H), 4.62 (s, 1H), 4.31 (t, J=8.4 Hz, 2H), 4.24 (dd, J=20.4, 14.1 Hz, 3H), 3.66 (ddd, J=14.6, 8.5, 6.1 Hz, 2H), 2.76 (t, J=11.9 Hz, 2H), 2.52 (s, 3H), 2.13-1.45 (m, 5H); MS (ESI(+)) m/e 456.3 (M+H)⁺.

Example 909 N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-1-(3-methylpyridazin-4-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting 1-(3-methylpyridazin-4-yl)-N-(4-(piperidin-4-yl)phenyl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2-fluorobenzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.08 (s, 1H), 8.55 (d, J=5.8 Hz, 1H), 7.76-7.24 (m, 8H), 6.45 (d, J=5.8 Hz, 1H), 4.50-4.45 (m, 1H), 4.32 (t, J=8.3 Hz, 2H), 4.23 (d, J=13.9 Hz, 2H), 3.73-3.62 (m, 1H), 3.50-3.41 (m, 1H), 3.26-3.07 (m, 2H), 2.94-2.56 (m, 3H), 2.45-1.03 (m, 5H; MS (ESI(+)) m/e 474.2 (M+H)⁺.

Example 910 N-(4-{1-[(2-aminopyridin-3-yl)carbonyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(4-(piperidin-4-yl)phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2-aminonicotinic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.04 (s, 1H), 8.56 (dd, J=4.5, 1.1 Hz, 1H), 8.00 (dd, J=4.9, 1.8 Hz, 1H), 7.54 (d, J=8.5 Hz, 2H), 7.46-7.32 (m, 2H), 7.21 (d, J=8.5 Hz, 2H), 6.83 (dd, J=9.0, 1.2 Hz, 1H), 6.59 (dd, J=7.3, 4.9 Hz, 1H), 5.92 (s, 2H), 4.24 (t, J=8.3 Hz, 2H), 4.14 (dd, J=8.0, 6.0 Hz, 2H), 4.09-3.84 (m, 2H), 3.73 (tt, J=8.5, 6.0 Hz, 1H), 2.99 (bs, 2H), 2.74 (tt, J=11.7, 3.2 Hz, 1H), 1.76 (d, J=11.8 Hz, 2H), 1.70-1.52 (m, 2H); MS (ESI(+)) m/e 458 (M+H)⁺.

Example 911 1-methyl-5-[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-1H-pyrazole-3-carboxylic acid

Ethyl 1-methyl-5-(4-(1-(pyridazin-3-yl)azetidine-3-carboxamido)phenyl)-1H-pyrazole-3-carboxylate (368 mg, 0.905 mmol) was taken up in tetrahydrofuran (3.38 mL), and methanol (3.38 mL) then 1N aqueous lithium hydroxide (1.35 mL, 1.350 mmol) was added. The mixture was heated at 60° C. for 2 hours. The mixture was concentrated to dryness, suspended in water and treated with 1N aqueous HCl to pH 2. The solution was extracted with ethyl acetate and the organic layers were dried with sodium sulfate, filtered, and concentrated to give a colorless syrup that solidified upon standing. This solid was triturated with ether and collected by filtration to give the title compound. ¹H NMR (400 MHz, DMSO-d6) δ ppm 12.67 (s, 1H), 10.32 (bs, 1H), 8.60-8.55 (m, 1H), 7.77 (d, J=8.4 Hz, 2H), 7.54 (d, J=8.4 Hz, 2H), 7.42 (dd, J=9.0, 4.5 Hz, 1H), 6.89 (d, J=8.9 Hz, 1H), 6.80 (s, 1H), 4.34-4.13 (m, 4H), 3.91 (s, 3H), 3.83-3.74 (m, 1H); MS (ESI(+)) m/e 379 (M+H)⁺.

Example 912 ethyl 1-methyl-5-[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-1H-pyrazole-3-carboxylate Example 912A ethyl 4-(4-nitrophenyl)-2,4-dioxobutanoate

-   1-(4-Nitrophenyl)ethanone (2 g, 12.11 mmol) was dissolved in     tetrahydrofuran (20 mL) and chilled to 0° C. Sodium ethanolate (21%     in ethanol) (7.85 g, 24.22 mmol) was added dropwise and the     resulting solution was stirred for 15 minutes at 0° C. Diethyl     oxylate (1.947 g, 13.32 mmol) was added dropwise and the ice bath     was removed. The mixture was stirred at room temperature for 3 hours     and diluted with 1N aqueous HCl (125 mL). The resulting suspension     was stirred for 30 minutes and collected by filtration to give the     title compound.

Example 912B ethyl 1-methyl-5-(4-nitrophenyl)-1H-pyrazole-3-carboxylate

Ethyl 4-(4-nitrophenyl)-2,4-dioxobutanoate (500 mg, 1.885 mmol) was dissolved in hexafluoroisopropanol (4 ml) and methylhydrazine (87 mg, 1.885 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 3 hours, concentrated to dryness, triturated with ether; and filtered to provide the title compound.

Example 912C ethyl 5-(4-aminophenyl)-1-methyl-1H-pyrazole-3-carboxylate

The title compound was prepared as described in Example 1B, substituting ethyl 1-methyl-5-(4-nitrophenyl)-1H-pyrazole-3-carboxylate for tert-butyl 4-(4-(1-(benzyloxycarbonyl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 912D ethyl 1-methyl-5-[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)phenyl]-1H-pyrazole-3-carboxylate

The title compound was prepared as described in Example 1A, substituting ethyl 5-(4-aminophenyl)-1-methyl-1H-pyrazole-3-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 1-(pyridazin-3-yl)azetidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.31 (s, 1H), 8.57 (dd, J=4.5, 1.3 Hz, 1H), 7.77 (d, J=8.7 Hz, 2H), 7.54 (d, J=8.6 Hz, 2H), 7.39 (dd, J=8.9, 4.5 Hz, 1H), 6.84 (s, 1H), 6.84 (dd, J=9.0, 1.4 Hz, 1H), 4.32-4.22 (m, 4H), 4.18 (dd, J=8.1, 5.8 Hz, 2H), 3.92 (s, 3H), 3.84-3.72 (m, 1H), 1.30 (t, J=7.1 Hz, 3H); MS (ESI(+)) m/e 407 (M+H)⁺.

Example 913

The title compound was prepared as described in Example 912, substituting phenylhydrazine for methylhydrazine in Example 912B. ¹H NMR (500 MHz, DMSO-d₆) δ ppm 10.24 (s, 1H), 8.56 (dd, J=4.5, 1.3 Hz, 1H), 7.60 (d, J=8.7 Hz, 2H), 7.51-7.41 (m, 3H), 7.38 (dd, J=9.0, 4.5 Hz, 1H), 7.34-7.30 (m, 2H), 7.20 (d, J=8.7 Hz, 2H), 7.08 (s, 1H), 6.82 (dd, J=9.0, 1.3 Hz, 1H), 4.33 (q, J=7.1 Hz, 2H), 4.24 (t, J=8.4 Hz, 2H), 4.14 (dd, J=8.0, 6.0 Hz, 2H), 3.77-3.69 (m, 1H), 1.32 (t, J=7.1 Hz, 3H); MS (ESI(+)) m/e 469 (M+H)⁺.

Example 914 N-{6[1-(2-fluorobenzoyl)piperidin-4-yl]pyridin-3-yl}-1-(pyridazin-3-yl)azetidine-3-carboxamide Example 914A tert-butyl 4-(5-(1-(pyridazin-3-yl)azetidine-3-carboxamido)pyridin-2-yl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting tert-butyl 4-(5-aminopyridin-2-yl)piperidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 1-(pyridazin-3-yl)azetidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 914B N-(6-(piperidin-4-yl)pyridin-3-yl)-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting tert-butyl 4-(5-(1-(pyridazin-3-yl)azetidine-3-carboxamido)pyridin-2-yl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 914C N-{6[1-(2-fluorobenzoyl)piperidin-4-yl]pyridin-3-yl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(6-(piperidin-4-yl)pyridin-3-yl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2-fluorobenzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.27 (s, 1H), 8.67 (d, J=2.5 Hz, 1H), 8.57 (dd, J=4.5, 1.2 Hz, 1H), 8.01 (dd, J=8.5, 2.5 Hz, 1H), 7.56-7.46 (m, 1H), 7.46-7.35 (m, 2H), 7.35-7.23 (m, 3H), 6.83 (dd, J=9.0, 1.2 Hz, 1H), 4.64 (d, J=13.0 Hz, 1H), 4.26 (t, J=8.4 Hz, 2H), 4.16 (dd, J=8.0, 6.0 Hz, 2H), 3.76 (tt, J=8.5, 5.9 Hz, 1H), 3.47 (d, J=12.6 Hz, 1H), 3.19 (t, J=12.3 Hz, 1H), 3.01-2.85 (m, 2H), 1.94 (d, J=13.0 Hz, 1H), 1.79 (d, J=12.1 Hz, 1H), 1.73-1.53 (m, 2H); MS (ESI(+)) m/e 461 (M+H)⁺.

Example 915 N-(4-{[(3R)-1-(3-methylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide Example 915A (R)-tert-butyl 3-(4-(1-(6-methylpyridazin-3-yl)azetidine-3-carboxamido)phenoxy)pyrrolidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting (R)-tert-butyl 3-(4-aminophenoxyl)pyrrolidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 1-(6-methylpyridazin-3-yl)azetidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 915B (R)-1-(6-methylpyridazin-3-yl)-N-(4-(pyrrolidin-3-yloxy)phenyl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting (R)-tert-butyl 3-(4-(1-(6-methylpyridazin-3-yl)azetidine-3-carboxamido)phenoxy)pyrrolidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 915C N-(4-{[(3R)-1-(3-methylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting (R)-1-(6-methylpyridazin-3-yl)-N-(4-(pyrrolidin-3-yloxy)phenyl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 3-methylbutanoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆, T=90° C.) 0.3 ppm 9.63 (s, 1H), 7.49 (d, J=8.9 Hz, 2H), 7.21 (d, J=9.0 Hz, 1H), 6.88 (d, J=8.7 Hz, 2H), 6.71 (d, J=9.0 Hz, 1H), 5.03-4.85 (m, 1H), 4.16 (dt, J=14.0, 8.0 Hz, 4H), 3.69 (tt, J=8.5, 6.1 Hz, 1H), 3.62-3.34 (m, 3H), 2.43 (s, 3H), 2.23-1.98 (m, 6H), 0.91 (d, J=6.2 Hz, 6H); MS (ESI(+)) m/e 438 (M+H)⁺.

Example 916 N-(4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting (R)-1-(6-methylpyridazin-3-yl)-N-(4-(pyrrolidin-3-yloxy)phenyl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and isobutyric acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆, T=90° C.) δ ppm 9.63 (s, 1H), 7.50 (d, J=9.0 Hz, 2H), 7.21 (d, J=9.0 Hz, 1H), 6.88 (d, J=8.9 Hz, 2H), 6.71 (d, J=9.0 Hz, 1H), 5.01-4.86 (m, 1H), 4.23-4.10 (m, 4H), 3.74-3.64 (m, 1H), 3.64-3.40 (m, 4H), 2.72-2.58 (m, 1H), 2.43 (s, 3H), 2.26-1.98 (m, 2H), 1.03 (dd, J=9.7, 4.0 Hz, 6H); MS (ESI(+)) m/e 424 (M+H)⁺.

Example 917 N-(4-{[(3R)-1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]oxy}phenyl)-1-(6-methylpyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting (R)-1-(6-methylpyridazin-3-yl)-N-(4-(pyrrolidin-3-yloxy)phenyl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2,4-difluorobenzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆, T=90° C.) δ ppm 9.63 (bs, 1H), 7.53-7.44 (m, 3H), 7.25-7.18 (m, 2H), 7.14-7.03 (m, 1H), 6.95-6.80 (m, 2H), 6.71 (d, J=8.9 Hz, 1H), 5.05-4.92 (m, 1H), 4.19 (t, J=8.2 Hz, 2H), 4.13 (t, J=7.0 Hz, 2H), 3.68 (tdd, J=10.3, 5.0, 1.7 Hz, 1H), 3.82-3.22 (m, 4H), 2.43 (s, 3H), 2.32-2.05 (m, 2H); MS (ESI(+)) m/e 494 (M+H)⁺.

Example 918 1-(6-methylpyridazin-3-yl)-N-(4-{[(3R)-1-(1,3-thiazol-4-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting (R)-1-(6-methylpyridazin-3-yl)-N-(4-(pyrrolidin-3-yloxy)phenyl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and thiazole-4-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆, T=90° C.) δ ppm 9.63 (s, 1H), 9.09 (d, J=1.6 Hz, 1H), 8.19 (d, J=2.0 Hz, 1H), 7.49 (d, J=8.7 Hz, 2H), 7.21 (d, J=9.0 Hz, 1H), 6.89 (d, J=8.6 Hz, 2H), 6.71 (d, J=9.0 Hz, 1H), 5.00 (dt, J=4.5, 2.2 Hz, 1H), 4.16 (dt, J=14.0, 8.0 Hz, 4H), 4.09-3.57 (m, 4H), 3.69 (tt, J=8.4, 6.1 Hz, 1H), 2.43 (s, 3H), 2.20 (dd, J=33.6, 24.3 Hz, 2H); MS (ESI(+)) m/e 465.2 (M+H)⁺.

Example 919 1-(pyridazin-3-yl)-N-{6-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]pyridin-3-yl}azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(6-(piperidin-4-yl)pyridin-3-yl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 4,4,4-trifluorobutanoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.27 (s, 1H), 8.67 (d, J=2.6 Hz, 1H), 8.57 (dd, J=4.5, 1.3 Hz, 1H), 8.00 (dd, J=8.5, 2.6 Hz, 1H), 7.40 (dd, J=9.0, 4.5 Hz, 1H), 7.26 (d, J=8.5 Hz, 1H), 6.86 (dd, J=9.0, 1.3 Hz, 1H), 4.50 (d, J=13.0 Hz, 1H), 4.26 (t, J=8.4 Hz, 2H), 4.17 (dd, J=8.2, 5.9 Hz, 2H), 3.97 (d, J=13.6 Hz, 1H), 3.76 (tt, J=8.6, 5.9 Hz, 1H), 3.11 (dd, J=18.5, 7.6 Hz, 1H), 2.90 (tt, J=11.7, 3.6 Hz, 1H), 2.76-2.59 (m, 2H), 2.59-2.43 (m, 2H), 1.91-1.77 (m, 2H), 1.66 (qd, J=12.6, 4.0 Hz, 1H), 1.51 (qd, J=12.7, 4.1 Hz, 1H); MS (ESI(+)) m/e 463 (M+H)⁺.

Example 920 N-{6-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]pyridin-3-yl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(6-(piperidin-4-yl)pyridin-3-yl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 3,3-dimethylbutanoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.26 (s, 1H), 8.66 (d, J=2.5 Hz, 1H), 8.57 (dd, J=4.5, 1.1 Hz, 1H), 8.00 (dd, J=8.5, 2.6 Hz, 1H), 7.38 (dd, J=9.0, 4.5 Hz, 1H), 7.25 (d, J=8.5 Hz, 1H), 6.83 (dd, J=9.0, 1.2 Hz, 1H), 4.58 (d, J=12.9 Hz, 1H), 4.26 (t, J=8.4 Hz, 2H), 4.16 (dd, J=8.0, 6.0 Hz, 2H), 4.07 (d, J=13.4 Hz, 1H), 3.76 (tt, J=8.5, 5.9 Hz, 1H), 3.10 (t, J=12.1 Hz, 1H), 2.88 (tt, J=11.7, 3.6 Hz, 1H), 2.59 (t, J=11.8 Hz, 1H), 2.29 (d, J=14.0 Hz, 1H), 2.22 (d, J=14.0 Hz, 1H), 1.84 (t, J=10.8 Hz, 2H), 1.60 (qd, J=12.7, 3.8 Hz, 1H), 1.48 (qd, J=12.7, 4.0 Hz, 1H), 1.00 (s, 9H); MS (ESI(+)) m/e 437 (M+H)⁺.

Example 921 (3S)—N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(4-methylpyridazin-3-yl)pyrrolidine-3-carboxamide Example 921A (S)-tert-butyl 4-(4-(1-(4-methylpyridazin-3-yl)pyrrolidine-3-carboxamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1C, substituting 3-chloro-4-methylpyridazine for 3-bromopyridine and (S)-tert-butyl 4-(4-(pyrrolidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 921B (S)-1-(4-methylpyridazin-3-yl)-N-(4-(piperidin-4-yl)phenyl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting (S)-tert-butyl 4-(4-(1-(4-methylpyridazin-3-yl)pyrrolidine-3-carboxamido)phenyl)piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 921C (3S)—N-[4-(1-benzoylpiperidin-4-yl)phenyl]-1-(4-methylpyridazin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting (S)-1-(4-methylpyridazin-3-yl)-N-(4-(piperidin-4-yl)phenyl)pyrrolidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and benzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.03 (s, 1H), 8.46 (d, J=4.6 Hz, 1H), 7.58-7.52 (m, 2H), 7.50-7.37 (m, 5H), 7.28-7.15 (m, 3H), 4.71-4.55 (m, 1H), 3.89-3.38 (m, 5H), 3.28-2.58 (m, 4H), 2.34 (s, 3H), 2.32-1.98 (m, 2H), 2.00-1.49 (m, 4H); MS (ESI(+)) m/e 470.2 (M+H)⁺.

Example 922 (3S)—N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-1-(4-methylpyridazin-3-yl)pyrrolidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting (S)-1-(4-methylpyridazin-3-yl)-N-(4-(piperidin-4-yl)phenyl)pyrrolidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2,2-dimethylpropanoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.02 (s, 1H), 8.46 (d, J=4.6 Hz, 1H), 7.57-7.51 (m, 2H), 7.22-7.13 (m, 3H), 4.45-4.36 (m, 2H), 3.85-3.72 (m, 2H), 3.68 (dd, J=7.9, 5.7 Hz, 2H), 3.21 (p, J=7.7 Hz, 1H), 2.93-2.66 (m, 3H), 2.34 (s, 3H), 2.31-2.05 (m, 2H), 1.82-1.74 (m, 2H), 1.53-1.34 (m, 2H), 1.22 (s, 9H); MS (ESI(+)) m/e 450.3 (M+H)⁺.

Example 923 N-{4-[1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 805, substituting 3,3,3-trifluoroprop-1-yne for ethynylcyclopropane in Example 805A and phenylhydrazine for methylhydrazine in Example 805B. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.26 (s, 1H), 8.56 (dd, J=4.5, 1.3 Hz, 1H), 7.61 (d, J=8.7 Hz, 2H), 7.50-7.44 (m, 3H), 7.41-7.31 (m, 3H), 7.23 (d, J=8.7 Hz, 2H), 7.14 (s, 1H), 6.83 (dd, J=8.9, 1.4 Hz, 1H), 4.24 (t, J=8.3 Hz, 2H), 4.14 (dd, J=8.1, 5.8 Hz, 2H), 3.74 (tt, J=8.5, 5.8 Hz, 1H); MS (ESI(+)) m/e 465.1 (M+H)⁺.

Example 924 N-{6-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]pyridin-3-yl}-1-(pyridazin-3-yl)azetidine-3-carboxamide Example 924A N-(6-chloropyridin-3-yl)-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting 6-chloropyridin-3-amine for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 1-(pyridazin-3-yl)azetidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 924B N-{6-[1-(2,2-dimethylpropyl)-1H-pyrazol-4-yl]pyridin-3-yl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described as described in Example 148A, substituting N-(6-chloropyridin-3-yl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for 4-bromoaniline and 1-neopentyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.31 (s, 1H), 8.69 (d, J=2.6 Hz, 1H), 8.57 (dd, J=4.5, 1.3 Hz, 1H), 8.18 (s, 1H), 8.06 (dd, J=8.6, 2.6 Hz, 1H), 7.95 (d, J=0.4 Hz, 1H), 7.63 (dd, J=8.6, 0.4 Hz, 1H), 7.39 (dd, J=8.9, 4.5 Hz, 1H), 6.84 (dd, J=9.0, 1.4 Hz, 1H), 4.27 (t, J=8.4 Hz, 2H), 4.18 (dd, J=8.2, 5.9 Hz, 2H), 3.94 (s, 2H), 3.78 (tt, J=8.6, 5.9 Hz, 1H), 0.93 (s, 9H); MS (ESI(+)) m/e 392 (M+H)⁺.

Example 925 tert-butyl 4-[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)-1H-pyrazol-1-yl]piperidine-1-carboxylate

The title compound was prepared as described in Example 1A, substituting tert-butyl 4-(4-amino-1H-pyrazol-1-yl)piperidine-1-carboxylate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 1-(pyridazin-3-yl)azetidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.15 (s, 1H), 8.56 (dd, J=4.5, 1.3 Hz, 1H), 7.98-7.90 (m, 1H), 7.47 (d, J=0.5 Hz, 1H), 7.38 (dd, J=9.0, 4.5 Hz, 1H), 6.82 (dd, J=9.0, 1.4 Hz, 1H), 4.31 (tt, J=11.3, 3.9 Hz, 1H), 4.22 (t, J=8.3 Hz, 2H), 4.12 (dd, J=8.1, 6.0 Hz, 2H), 4.02 (d, J=12.3 Hz, 2H), 3.67 (tt, J=8.6, 6.0 Hz, 1H), 2.88 (bs, 2H), 1.95 (dd, J=12.4, 2.4 Hz, 2H), 1.74 (qd, J=12.4, 4.4 Hz, 2H), 1.41 (s, 9H); MS (ESI(+)) m/e 428 (M+H)⁺.

Example 926 N-(6-{1[(4-methylpiperidin-4-yl)methyl]-1H-pyrazol-4-yl}pyridin-yl)-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described as described in Example 148A, substituting N-(6-chloropyridin-3-yl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for 4-bromoaniline and tert-butyl 4-methyl-4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)methyl)piperidine-1-carboxylate for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole followed by TFA deprotection as described in Example 1D to give the title compound as a TFA salt. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.63 (s, 1H), 8.79 (d, J=2.5 Hz, 1H), 8.67-8.54 (m, 2H), 8.52-8.39 (m, 1H), 8.31 (s, 1H), 8.13 (dd, J=8.7, 2.5 Hz, 1H), 8.05 (s, 1H), 7.84 (dd, J=9.4, 4.4 Hz, 1H), 7.76 (d, J=8.7 Hz, 1H), 7.51 (dd, J=9.4, 0.9 Hz, 1H), 4.51 (t, J=9.3 Hz, 2H), 4.44 (dd, J=9.5, 5.9 Hz, 2H), 4.14 (s, 2H), 3.87 (tt, J=8.8, 5.9 Hz, 1H), 3.29-3.14 (m, 2H), 3.14-2.96 (m, 2H), 1.74-1.58 (m, 2H), 1.56-1.42 (m, 2H), 0.98 (s, 3H); MS (ESI(+)) m/e 433 (M+H)⁺.

Example 969 N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-1-(4-methylpyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting 1-(4-methylpyridazin-3-yl)-N-(4-(piperidin-4-yl)phenyl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 3,3-dimethylbutanoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.02 (s, 1H), 8.49 (d, J=4.6 Hz, 1H), 7.57-7.51 (m, 2H), 7.22-7.14 (m, 3H), 4.65-4.57 (m, 1H), 4.39-4.24 (m, 4H), 4.12-4.03 (m, 1H), 3.68 (p, J=7.4 Hz, 1H), 3.07 (t, J=12.0 Hz, 1H), 2.77-2.64 (m, 1H), 2.34-2.26 (m, 1H), 2.25-2.16 (m, 4H), 2.12-1.56 (m, 2H), 1.58-1.07 (m, 3H), 1.09-0.87 (m, 9H); MS (ESI(+)) m/e 450.3 (M+H)⁺.

Example 970 N-{1-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-1H-pyrazol-4-yl}-1-(pyridazin-3-yl)azetidine-3-carboxamide Example 970A N-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting tert-butyl 4-[4-({[1-(pyridazin-3-yl)azetidin-3-yl]carbonyl}amino)-1H-pyrazol-1-yl]piperidine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate.

Example 970B N-{1-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]-1H-pyrazol-4-yl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 3,3-dimethylbutanoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (500 MHz, DMSO-d₆) δ ppm 10.16 (s, 1H), 8.56 (dd, J=4.5, 1.1 Hz, 1H), 7.95 (s, 1H), 7.46 (s, 1H), 7.38 (dd, J=9.0, 4.5 Hz, 1H), 6.83 (dd, J=9.0, 1.2 Hz, 1H), 4.53 (d, J=13.3 Hz, 1H), 4.38 (tt, J=11.3, 4.0 Hz, 1H), 4.23 (t, J=8.3 Hz, 2H), 4.12 (dd, J=8.0, 6.1 Hz, 2H), 4.07 (d, J=13.6 Hz, 1H), 3.67 (tt, J=8.5, 6.0 Hz, 1H), 3.15 (t, J=12.1 Hz, 1H), 2.66 (t, J=11.9 Hz, 1H), 2.30 (d, J=14.1 Hz, 1H), 2.23 (d, J=14.1 Hz, 1H), 1.98 (t, J=10.7 Hz, 2H), 1.80 (qd, J=12.3, 4.1 Hz, 1H), 1.68 (qd, J=12.3, 4.2 Hz, 1H), 1.00 (s, 9H); MS (ESI(+)) m/e 426 (M+H)⁺.

Example 971 N-{1-[1-(2-fluorobenzoyl)piperidin-4-yl]-1H-pyrazol-4-yl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2-fluorobenzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.15 (s, 1H), 8.56 (dd, J=4.5, 1.3 Hz, 1H), 7.98 (s, 1H), 7.54-7.42 (m, 3H), 7.38 (dd, J=9.0, 4.5 Hz, 1H), 7.34-7.26 (m, 2H), 6.82 (dd, J=9.0, 1.3 Hz, 1H), 4.59 (d, J=13.3 Hz, 1H), 4.45 (tt, J=11.2, 3.9 Hz, 1H), 4.23 (t, J=8.3 Hz, 2H), 4.12 (dd, J=8.0, 6.0 Hz, 2H), 3.67 (tt, J=8.5, 6.0 Hz, 1H), 3.47 (d, J=13.3 Hz, 1H), 3.22 (t, J=12.2 Hz, 1H), 2.98 (td, J=13.0, 2.7 Hz, 1H), 2.09 (d, J=11.2 Hz, 1H), 2.00-1.91 (m, 1H), 1.90-1.74 (m, 2H); MS (ESI(+)) m/e 450 (M+H)⁺.

Example 972 N-[4-(phenylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide Example 972A methyl 4-(1-(pyridazin-3-yl)azetidine-3-carboxamido)benzoate

The title compound was prepared as described in Example 1A, substituting methyl 4-aminobenzoate for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 1-(pyridazin-3-yl)azetidine-3-carboxylic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid.

Example 972B 4-(1-(pyridazin-3-yl)azetidine-3-carboxamido)benzoic acid

The procedure was followed as described in Example 911, substituting methyl 4-(1-(pyridazin-3-yl)azetidine-3-carboxamido)benzoate for ethyl 1-methyl-5-(4-(1-(pyridazin-3-yl)azetidine-3-carboxamido)phenyl)-1H-pyrazole-3-carboxylate.

Example 972C N-[4-(phenylcarbamoyl)phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting aniline for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 4-(1-(pyridazin-3-yl)azetidine-3-carboxamido)benzoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid. ¹H NMR (400 MHz, DMSO-d₆/D₂O) δ ppm 8.53 (dd, J=4.4, 1.3 Hz, 1H), 7.98-7.92 (m, 2H), 7.77-7.65 (m, 5H), 7.38-7.24 (m, 3H), 7.15-7.07 (m, 1H), 4.49 (t, J=9.0 Hz, 2H), 4.46-4.38 (m, 2H), 4.00-3.81 (m, 1H); MS (ESI(+)) m/e 374 (M+H)⁺.

The following Examples were essentially prepared as described in Example 972, substituting an appropriate amine in Example 972C. Some products were purified by flash chromatography while others were purified by reverse-phase HPLC. Accordingly, some Examples were isolated as trifluoroacetic acid salts.

TABLE 23 Ex Name MS 973 N-{4-[(2,2-dimethylpropyl)carbamoyl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 368 (M + H)⁺ 974 N-{4-(3-methoxy-2,2-dimethylpropyl)carbamoyl] (ESI(+)) phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 398 (M + H)⁺ 975 N-{4-[(2-cyclopropylethyl)carbamoyl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e XXX (M + H)⁺ 976 N-(4-{[2-(2-ethylpiperidin-1-yl)ethyl]carbamoyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 366 (M + H)⁺ 977 N-{4-(cyclobutylmethyl)carbamoyl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 366 (M + H)⁺ 978 N-{4-[(2S)-butan-2-ylcarbamoyl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 354 (M + H)⁺ 979 N-[4-(butylcarbamoyl)phenyl]-1-(pyridazin-3-yl) (ESI(+)) azetidine-3-carboxamide m/e 354 (M + H)⁺ 980 N-{4-[(2,2-dimethyltetrahydro-2H-pyran-4-yl) (ESI(+)) carbamoyl]phenyl}-1-(pyridazin-3-yl)azetidine-3- m/e 410 carboxamide (M + H)⁺ 981 N-(4-{[(1S)-1-cyclopropylethyl]carbamoyl}phenyl)-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 366 (M + H)⁺ 982 N-[4-({2-methyl(phenyl)amino]ethyl}carbamoyl) (ESI(+)) phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 430 (M + H)⁺ 983 N-{4-[1,1′-bi(cyclopropyl)-1-ylcarbamoyl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 378 (M + H)⁺ 984 1-(pyridazin-3-yl)-N-[4-(thiophen-3-ylcarbamoyl) (ESI(+)) phenyl]azetidine-3-carboxamide m/e 366 (M + H)⁺ 985 N-(4-{[(1R)-1-cyclopropylethyl]carbamoyl}phenyl)-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 366 (M + H)⁺ 986 N-{4-[(1-methylpiperidin-4-yl)carbamoyl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 395 (M + H)⁺ 987 N-{4-[(2R)-butan-2-ylcarbamoyl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 354 (M + H)⁺ 988 N-[4-(1-azabicyclo[2.2.2]oct-3-ylcarbamoly)phenyl]-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 407 (M + H)⁺ 989 1-(pyridazin-3-yl)-N-{4-[(tetrahydrofuran-3- (ESI(+)) ylmethyl)carbamoyl]phenyl}azetidine-3-carboxamide m/e 382 (M + H)⁺ 990 N-{4-[(oxetan-3-ylmethyl)carbamoyl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 368 (M + H)⁺ 991 N-{4-[(2-methylcyclopropyl)carbamoyl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 352 (M + H)⁺ 992 N-[4-(cyclobutylcarbamoyl)phenyl]-1-(pyridazin-3-yl) (ESI(+)) azetidine-3-carboxamide m/e 352 (M + H)⁺ 993 N-{4-[(1-methylcyclopropyl)carbamoyl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 352 (M + H)⁺ 994 N-{4-[(2-methoxy-2-methylpropyl)carbamoyl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 384 (M + H)⁺ 995 N-{4-[(cyclopropylmethyl)carbamoyl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 352 (M + H)⁺ 996 1-(pyridazin-3-yl)-N-(4-{[(2R)-tetrahydrofuran-2- (ESI(+)) ylmethyl]carbamoyl}phenyl)azetidine-3-carboxamide m/e 382 (M + H)⁺ 997 1-(pyridazin-3-yl)-N-{4-[(3,3,3- (ESI(+)) trifluoropropyl)carbamoyl]phenyl}azetidine-3- m/e 394 carboxamide (M + H)⁺ 998 N-{4-[(1-methylpiperidin-3-yl)carbamoyl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 395 (M + H)⁺ 999 N-(4-{[(3-methyloxetan-3-yl)methyl]carbamoyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 382 (M + H)⁺ 1000 1-(pyridazin-3-yl)-N-(4-{[(2S)-tetrahydrofuran-2- (ESI(+)) ylmethyl]carbamoyl}phenyl)azetidine-3-carboxamide m/e 382 (M + H)⁺ 1001 1-(pyridazin-3-yl)-N-{4-[(tetrahydro-2H-pyran-4- (ESI(+)) ylmethyl)carbamoyl]phenyl}azetidine-3-carboxamide m/e 396 (M + H)⁺ 1002 1-(pyridazin-3-yl)-N-[4-(tetrahydro-2H-pyran-4- (ESI(+)) ylcarbamoyl)phenyl]azetidine-3-carboxamide m/e 382 (M + H)⁺ 1003 N-(4-{[(1-methylpiperidin-3-yl)methyl]carbamoyl} (ESI(+)) phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 409 (M + H)⁺ 1004 N-[4-(cyclopropylcarbamoyl)phenyl]-1-(pyridazin-3-yl) (ESI(+)) azetidine-3-carboxamide m/e 338 (M + H)⁺ 1005 N-[4-(cyclopentylcarbamoyl)phenyl]-1-(pyridazin-3-yl) (ESI(+)) azetidine-3-carboxamide m/e 366 (M + H)⁺ 1006 N-[4-(benzylcarbamoyl)phenyl]-1-(pyridazin-3-yl) (ESI(+)) azetidine-3-carboxamide m/e 388 (M + H)⁺ 1007 N-{4-[(3-fluorophenyl)carbamoyl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 392 (M + H)⁺ 1008 N-[4-(propylcarbamoyl)phenyl]-1-(pyridazin-3-yl) (ESI(+)) azetidine-3-carboxamide m/e 340 (M + H)⁺ 1009 N-{4-[(4-fluorophenyl)carbamoyl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 392 (M + H)⁺ 1010 N-{4-[(2-fluorophenyl)carbamoyl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 392 (M + H)⁺ 1011 N-{4-[(1-methylcyclobutyl)carbamoyl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 366 (M + H)⁺ 1012 N-[4-(prop-2-en-1-ylcarbamoyl)phenyl-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 338 (M + H)⁺ 1020 1-(pyridazin-3-yl)-N-{4-(3S)-tetrahydrofuran-3- (ESI(+)) ylcarbamoyl]phenyl}azetidine-3-carboxamide m/e 368 (M + H)⁺ 1021 N-[4-({4-[2-(dimethylamino)ethyl]phenyl}carbamoyl) (ESI(+)) phenyl]-1-(pyridazin-3-yl)azetidine-3-carboxamide m/e 445 (M + H)⁺ 1022 1-(pyridazin-3-yl)-N-{4-[(3R)-tetrahydrofuran-3- (ESI(+)) ylcarbamoyl]phenyl}azetidine-3-carboxamide m/e 368 (M + H)⁺ 1023 N-{4-[(2-methoxyethyl)carbamoyl]phenyl}-1- (ESI(+)) (pyridazin-3-yl)azetidine-3-carboxamide m/e 356 (M + H)⁺

Example 1024 N-{4-[1-(3-amino-2,2-dimethylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide Example 1024A tert-butyl (2,2-dimethyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propyl)carbamate

A solution of tert-butyl (3-hydroxy-2,2-dimethylpropyl)carbamate (1.000 g, 4.92 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1.145 g, 5.90 mmol) and 2-(tributylphosphoranylidene)acetonitrile (1.425 g, 5.90 mmol) were stirred together in toluene (20 ml) at 90° C. overnight. The reaction mixture was concentrated and purified by normal phase chromatography to give the title compound.

Example 1024B tert-butyl (2,2-dimethyl-3-(4-(4-(1-(pyridazin-3-yl)azetidine-3-carboxamido)phenyl)-1H-pyrazol-1-yl)propyl)carbamate

The title compound was prepared as described as described in Example 148A, substituting N-(4-bromophenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for 4-bromoaniline and tert-butyl (2,2-dimethyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propyl)carbamate for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.

Example 1024C N-{4-[1-(3-amino-2,2-dimethylpropyl)-1H-pyrazol-4-yl]phenyl}-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting tert-butyl (2,2-dimethyl-3-(4-(4-(1-(pyridazin-3-yl)azetidine-3-carboxamido)phenyl)-1H-pyrazol-1-yl)propyl)carbamate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate to give the title compound as a TFA salt. ¹H NMR (500 MHz, DMSO-d₆) δ ppm 10.26 (s, 1H), 8.57 (dd, J=4.4, 1.1 Hz, 1H), 8.12 (s, 1H), 7.95 (bs, 3H), 7.92 (s, 1H), 7.74 (dd, J=9.3, 4.4 Hz, 1H), 7.64 (d, J=8.7 Hz, 2H), 7.55 (d, J=8.6 Hz, 2H), 7.36 (d, J=9.2 Hz, 1H), 4.44 (t, J=9.1 Hz, 2H), 4.37 (dd, J=9.2, 5.9 Hz, 2H), 4.10 (s, 2H), 3.81 (tt, J=8.8, 5.9 Hz, 1H), 2.83-2.70 (m, 2H), 0.96 (s, 6H); MS (ESI(+)) m/e 406 (M+H)⁺.

Example 1025 N-(4-{1-[2,2-dimethyl-3-(piperazin-1-yl)propyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide Example 1025A tert-butyl 4-(2,2-dimethyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1024A, substituting tert-butyl 4-(3-hydroxy-2,2-dimethylpropyl)piperidine-1-carboxylate for tert-butyl (3-hydroxy-2,2-dimethylpropyl)carbamate.

Example 1025B tert-butyl 4-(2,2-dimethyl-3-(4-(4-(1-(pyridazin-3-yl)azetidine-3-carboxamido)phenyl)-1H-pyrazol-1-yl)propyl)piperazine-1-carboxylate

The title compound was prepared as described as described in Example 148A, substituting N-(4-bromophenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for 4-bromoaniline and tert-butyl 4-(2,2-dimethyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propyl)piperidine-1-carboxylate for 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.

Example 1025C N-(4-{1-[2,2-dimethyl-3-(piperazin-1-yl)propyl]-1H-pyrazol-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1D, substituting tert-butyl 4-(2,2-dimethyl-3-(4-(4-(1-(pyridazin-3-yl)azetidine-3-carboxamido)phenyl)-1H-pyrazol-1-yl)propyl)piperazine-1-carboxylate for tert-butyl 4-(4-(1-(pyridin-3-yl)azetidine-3-carboxamido)phenoxy)piperidine-1-carboxylate to give the title compound as a TFA salt. ¹H NMR (500 MHz, DMSO-d₆) δ ppm 10.25 (s, 1H), 8.81 (s, 2H), 8.57 (dd, J=4.3, 1.0 Hz, 1H), 8.07 (s, 1H), 7.86 (s, 1H), 7.80 (dd, J=9.3, 4.4 Hz, 1H), 7.62 (d, J=8.7 Hz, 2H), 7.54 (d, J=8.6 Hz, 2H), 7.45 (d, J=8.9 Hz, 1H), 4.47 (t, J=9.2 Hz, 2H), 4.40 (dd, J=9.3, 5.9 Hz, 2H), 4.03 (s, 2H), 3.87-3.74 (m, 1H), 3.19 (s, 4H), 2.92 (s, 4H), 2.45 (s, 2H), 0.89 (s, 6H); MS (ESI(+)) m/e 475 (M+H)⁺.

Example 1026 N-(4-{1-[2-methyl-2-(piperazin-1-yl)propanoyl]piperidin-4-yl}phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide

The title compound was prepared as described in Example 1A, substituting N-(4-(piperidin-4-yl)phenyl)-1-(pyridazin-3-yl)azetidine-3-carboxamide for tert-butyl 4-(4-aminophenoxyl)piperidine-1-carboxylate and 2-(4-(tert-butoxycarbonyl)piperazin-1-yl)-2-methylpropanoic acid for 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid, followed by TFA deprotection as described in Example 1D to give the title compound as a TFA salt. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.17 (s, 1H), 8.67 (s, 2H), 8.56 (d, J=4.3 Hz, 1H), 7.77 (dd, J=9.3, 4.4 Hz, 1H), 7.55 (d, J=8.4 Hz, 2H), 7.42 (d, J=9.3 Hz, 1H), 7.21 (d, J=8.5 Hz, 2H), 5.27 (s, 1H), 4.59 (s, 1H), 4.45 (t, J=9.1 Hz, 2H), 4.37 (dd, J=9.2, 5.9 Hz, 2H), 3.91-3.71 (m, 1H), 3.11 (s, 5H), 2.81-2.53 (m, 6H), 1.80 (d, J=12.0 Hz, 2H), 1.45 (td, J=12.3, 9.1 Hz, 2H), 1.21 (s, 6H); MS (ESI(+)) m/e 492 (M+H)⁺. 

1-16. (canceled)
 17. A method of treating inflammatory and tissue repair disorders; particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, atherosclerosis, restenosis, diabetes, glomerulonephritis, cancer, particularly wherein the cancer is selected from breast, prostate, lung, colon, cervix, ovary, skin, CNS, bladder, pancreas, leukemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia in a patient, said method comprising administering to the patient a therapeutically effective amount of a compound of formula (IC), or a therapeutically acceptable salt thereof,

X¹ is N and X² is CR¹; or X¹ is CR¹ and X² is N; or X¹ is CR¹ and X² is CR¹; Y¹ is C(O)NH, or NHC(O); Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl; R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I; R² is independently selected from the group consisting of C₄-C₆-alkyl, C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl, and 5-6 membered heteroaryl; wherein each R² C₄-C₆-alkyl, C₄-C₆-alkenyl, and C₄-C₆-alkynyl is substituted with one or more substituents independently selected from the group consisting of R³, OR³, SR³, S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂, NHR³, N(R³)₂, NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³, NR³C(O)OR³, NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³, NR³C(O)N(R³)₂, C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³, C(O)NHSO₂R³, C(O)NR³SO₂R³ SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴ SO₂NH₂, SO₂NHR⁴ SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃ NO₂, F, Cl, and I; R³, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and heterocyclyl; wherein each R³ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁵, OR⁵, SR⁵, S(O)R⁵, SO₂R⁵, C(O)R⁵, CO(O)R⁵, OC(O)R⁵, OC(O)OR⁵, NH₂, NHR⁵, N(R⁵)₂, NHC(O)R⁵, NR⁵C(O)R⁵, NHS(O)₂R⁵, NR⁵S(O)₂R⁵, NHC(O)OR⁵, NR⁵C(O)OR⁵, NHC(O)NH₂, NHC(O)NHR⁵, NHC(O)N(R⁵)₂, NR⁵C(O)NHR⁵, NR⁵C(O)N(R⁵)₂, C(O)NH₂, C(O)NHR⁵, C(O)N(R⁵)₂, C(O)NHOH, C(O)NHOR⁵, C(O)NHSO₂R⁵, C(O)NR⁵SO₂R⁵, SO₂NH₂, SO₂NHR⁵, SO₂N(R⁵)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁵, C(N)N(R⁵)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R³ aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁶, OR⁶, SR⁶, S(O)R⁶, SO₂R⁶, C(O)R⁶, CO(O)R⁶, OC(O)R⁶, OC(O)OR⁶, NH₂, NHR⁶, N(R⁶)₂, NHC(O)R⁶, NR⁶C(O)R⁶, NHS(O)₂R⁶, NR⁶S(O)₂R⁶, NHC(O)OR⁶, NR⁶C(O)OR⁶, NHC(O)NH₂, NHC(O)NHR⁶, NHC(O)N(R⁶)₂, NR⁶C(O)NHR⁶, NR⁶C(O)N(R⁶)₂, C(O)NH₂, C(O)NHR⁶, C(O)N(R⁶)₂, C(O)NHOH, C(O)NHOR⁶, C(O)NHSO₂R⁶, C(O)NR⁶SO₂R⁶, SO₂NH₂, SO₂NHR⁶, SO₂N(R⁶)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁶, C(N)N(R⁶)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷ SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃OH, (O), CN, N₃, NO₂, F, Cl, Br and I; R⁵, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁵ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁸, OR⁸, SR⁸, S(O)R⁸, SO₂R⁸, NHR⁸, N(R⁸)₂, C(O)R⁸, C(O)NH₂, C(O)NHR⁸, C(O)N(R⁸)₂, NHC(O)R⁸, NR⁸C(O)R⁸, NHSO₂R⁸, NHC(O)OR⁸, SO₂NH₂, SO₂NHR⁸, SO₂N(R⁸)₂, NHC(O)NH₂, NHC(O)NHR⁸, OH, (O), C(O)OH, N₃, CN, NH₂, F, Cl, Br and I; R⁶, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁶ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁹, OR⁹, SR⁹, S(O)R⁹, SO₂R⁹, NHR⁹, N(R⁹)₂, C(O)R⁹, C(O)NH₂, C(O)NHR⁹, C(O)N(R⁹)₂, NHC(O)R⁹, NR⁹C(O)R⁹, NHSO₂R⁹, NHC(O)OR⁹, SO₂NH₂, SO₂NHR⁹, SO₂N(R⁹)₂, NHC(O)NH₂, NHC(O)NHR⁹, OH, (O), C(O)OH, N₃, CN, NH₂ CF₃, CF₂CF₃, F, Cl, Br and I; R⁷, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; R⁸, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; R⁹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein the cyclic moieties represented by R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹ are independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, C(O)C(O)R¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃ NO₂, CF₃, OCF₃, F, Cl, Br and I; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, OR¹³, C(O)OR¹³, OCF₃, CF₃, F, Cl, Br and I; R¹², at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; and R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; with the proviso that when X¹ is CR¹ and X² is CR¹; R¹ is hydrogen; Y¹ is NHC(O); Z¹ is

and R² is pyrrolyl; the R² pyrrolyl is not substituted with two alkyl groups.
 18. A method of treating inflammatory and tissue repair disorders; particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, atherosclerosis, restenosis, diabetes, glomerulonephritis, cancer, particularly wherein the cancer is selected from breast, prostate, lung, colon, cervix, ovary, skin, CNS, bladder, pancreas, leukemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia or spleen cancer in a patient, said method comprising administering to the patient therapeutically effective amount of the compound of formula (IC), or a therapeutically acceptable salt thereof,

X¹ is N and X² is CR¹; or X¹ is CR¹ and X² is N; or X¹ is CR¹ and X² is CR¹; Y¹ is C(O)NH, or NHC(O); Z¹ is

wherein

indicates the point of attachment to Y¹ and

indicates the point of attachment to the nitrogen containing heteroaryl; R¹, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I; R² is independently selected from the group consisting of C₄-C₆-alkyl, C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl, and 5-6 membered heteroaryl; wherein each R² C₄-C₆-alkyl, C₄-C₆-alkenyl, and C₄-C₆-alkynyl is substituted with one or more substituents independently selected from the group consisting of R³, OR³, SR³, S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂, NHR³, N(R³)₂, NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³, NR³C(O)OR³, NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³, NR³C(O)N(R³)₂, C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³, C(O)NHSO₂R³, C(O)NR³SO₂R³ SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R² aryl and 5-6 membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃ NO₂, F, Cl, and I; R³, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, and heterocyclyl; wherein each R³ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁵, OR⁵, SR⁵, S(O)R⁵, SO₂R⁵, C(O)R⁵, CO(O)R⁵, OC(O)R⁵, OC(O)OR⁵, NH₂, NHR⁵, N(R⁵)₂, NHC(O)R⁵, NR⁵C(O)R⁵, NHS(O)₂R⁵, NR⁵S(O)₂R⁵, NHC(O)OR⁵, NR⁵C(O)OR⁵, NHC(O)NH₂, NHC(O)NHR⁵, NHC(O)N(R⁵)₂, NR⁵C(O)NHR⁵, NR⁵C(O)N(R⁵)₂, C(O)NH₂, C(O)NHR⁵, C(O)N(R⁵)₂, C(O)NHOH, C(O)NHOR⁵, C(O)NHSO₂R⁵, C(O)NR⁵SO₂R⁵, SO₂NH₂, SO₂NHR⁵, SO₂N(R⁵)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁵, C(N)N(R⁵)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R³ aryl, cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁶, OR⁶, SR⁶, S(O)R⁶, SO₂R⁶, C(O)R⁶, CO(O)R⁶, OC(O)R⁶, OC(O)OR⁶, NH₂, NHR⁶, N(R⁶)₂, NHC(O)R⁶, NR⁶C(O)R⁶, NHS(O)₂R⁶, NR⁶S(O)₂R⁶, NHC(O)OR⁶, NR⁶C(O)OR⁶, NHC(O)NH₂, NHC(O)NHR⁶, NHC(O)N(R⁶)₂, NR⁶C(O)NHR⁶, NR⁶C(O)N(R⁶)₂, C(O)NH₂, C(O)NHR⁶, C(O)N(R⁶)₂, C(O)NHOH, C(O)NHOR⁶, C(O)NHSO₂R⁶, C(O)NR⁶SO₂R⁶, SO₂NH₂, SO₂NHR⁶, SO₂N(R⁶)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁶, C(N)N(R⁶)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R⁴, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷ SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; R⁵, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁵ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁸, OR⁸, SR⁸, S(O)R⁸, SO₂R⁸, NHR⁸, N(R⁸)₂, C(O)R⁸, C(O)NH₂, C(O)NHR⁸, C(O)N(R⁸)₂, NHC(O)R⁸, NR⁸C(O)R⁸, NHSO₂R⁸, NHC(O)OR⁸, SO₂NH₂, SO₂NHR⁸, SO₂N(R⁸)₂, NHC(O)NH₂, NHC(O)NHR⁸, OH, (O), C(O)OH, N₃, CN, NH₂, F, Cl, Br and I; R⁶, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R⁶ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R⁹, OR⁹, SR⁹, S(O)R⁹, SO₂R⁹, NHR⁹, N(R⁹)₂, C(O)R⁹, C(O)NH₂, C(O)NHR⁹, C(O)N(R⁹)₂, NHC(O)R⁹, NR⁹C(O)R⁹, NHSO₂R⁹, NHC(O)OR⁹, SO₂NH₂, SO₂NHR⁹, SO₂N(R⁹)₂, NHC(O)NH₂, NHC(O)NHR⁹, OH, (O), C(O)OH, N₃, CN, NH₂ CF₃, CF₂CF₃, F, Cl, Br and I; R⁷, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; R⁸, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; R⁹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein the cyclic moieties represented by R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹ are independently optionally substituted with one or more substituents independently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, C(O)C(O)R¹⁰, NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹⁰, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹ SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃ NO₂, CF₃, OCF₃, F, Cl, Br and I; R¹¹, at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl is optionally substituted with alkoxy or aryl; wherein each R¹¹ aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more substituents independently selected from the group consisting of R¹³, OR¹³, C(O)OR¹³, OCF₃, CF₃, F, Cl, Br and I; R¹², at each occurrence, is independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; and R¹³, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; with the proviso that when X¹ is CR¹ and X² is CR¹; R¹ is hydrogen; Y¹ is NHC(O); Z¹ is

and R² is pyrrolyl; the R² pyrrolyl is not substituted with two alkyl groups; and a therapeutically effective amount of one additional therapeutic agent or more than one additional therapeutic agent. 